Renal denervation for resistant hypertension

Anna Pisano; Luigi Francesco Iannone; Antonio Leo; Emilio Russo; Giuseppe Coppolino; Davide Bolignano

doi:10.1002/14651858.CD011499.pub3

. 2021 Nov 22;2021(11):CD011499. doi: 10.1002/14651858.CD011499.pub3

Renal denervation for resistant hypertension

Anna Pisano ¹, Luigi Francesco Iannone ², Antonio Leo ², Emilio Russo ², Giuseppe Coppolino ², Davide Bolignano ^3,^✉

Editor: Cochrane Hypertension Group

PMCID: PMC8607757 PMID: 34806762

Abstract

Background

Resistant hypertension is highly prevalent among the general hypertensive population and the clinical management of this condition remains problematic. Different approaches, including a more intensified antihypertensive therapy, lifestyle modifications or both, have largely failed to improve patients' outcomes and to reduce cardiovascular and renal risk. As renal sympathetic hyperactivity is a major driver of resistant hypertension, in the last decade renal sympathetic ablation (renal denervation) has been proposed as a possible therapeutic alternative to treat this condition.

Objectives

We sought to evaluate the short‐ and long‐term effects of renal denervation in individuals with resistant hypertension on clinical end points, including fatal and non‐fatal cardiovascular events, all‐cause mortality, hospital admissions, quality of life, blood pressure control, left ventricular hypertrophy, cardiovascular and metabolic profile and kidney function, as well as the potential adverse events related to the procedure.

Search methods

For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to 3 November 2020: Cochrane Hypertension’s Specialised Register, CENTRAL (2020, Issue 11), Ovid MEDLINE, and Ovid Embase. The World Health Organization International Clinical Trials Registry Platform (via CENTRAL) and the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov were searched for ongoing trials. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.

Selection criteria

We considered randomised controlled trials (RCTs) that compared renal denervation to standard therapy or sham procedure to treat resistant hypertension, without language restriction.

Data collection and analysis

Two authors independently extracted data and assessed study risk of bias. We summarised treatment effects on available clinical outcomes and adverse events using random‐effects meta‐analyses. We assessed heterogeneity in estimated treatment effects using Chi² and I² statistics. We calculated summary treatment estimates as a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, and a risk ratio (RR) for dichotomous outcomes, together with their 95% confidence intervals (CI). Certainty of evidence has been assessed using the GRADE approach.

Main results

We found 15 eligible studies (1416 participants). In four studies, renal denervation was compared to sham procedure; in the remaining studies, renal denervation was tested against standard or intensified antihypertensive therapy. Most studies had unclear or high risk of bias for allocation concealment and blinding.

When compared to control, there was low‐certainty evidence that renal denervation had little or no effect on the risk of myocardial infarction (4 studies, 742 participants; RR 1.31, 95% CI 0.45 to 3.84), ischaemic stroke (5 studies, 892 participants; RR 0.98, 95% CI 0.33 to 2.95), unstable angina (3 studies, 270 participants; RR 0.51, 95% CI 0.09 to 2.89) or hospitalisation (3 studies, 743 participants; RR 1.24, 95% CI 0.50 to 3.11). Based on moderate‐certainty evidence, renal denervation may reduce 24‐hour ambulatory blood pressure monitoring (ABPM) systolic BP (9 studies, 1045 participants; MD ‐5.29 mmHg, 95% CI ‐10.46 to ‐0.13), ABPM diastolic BP (8 studies, 1004 participants; MD ‐3.75 mmHg, 95% CI ‐7.10 to ‐0.39) and office diastolic BP (8 studies, 1049 participants; MD ‐4.61 mmHg, 95% CI ‐8.23 to ‐0.99). Conversely, this procedure had little or no effect on office systolic BP (10 studies, 1090 participants; MD ‐5.92 mmHg, 95% CI ‐12.94 to 1.10). Moderate‐certainty evidence suggested that renal denervation may not reduce serum creatinine (5 studies, 721 participants, MD 0.03 mg/dL, 95% CI ‐0.06 to 0.13) and may not increase the estimated glomerular filtration rate (eGFR) or creatinine clearance (6 studies, 822 participants; MD ‐2.56 mL/min, 95% CI ‐7.53 to 2.42).

Authors' conclusions

In patients with resistant hypertension, there is low‐certainty evidence that renal denervation does not improve major cardiovascular outomes and renal function. Conversely, moderate‐certainty evidence exists that it may improve 24h ABPM and diastolic office‐measured BP. Future trials measuring patient‐centred instead of surrogate outcomes, with longer follow‐up periods, larger sample size and more standardised procedural methods are necessary to clarify the utility of this procedure in this population.

Keywords: Humans, Antihypertensive Agents, Antihypertensive Agents/therapeutic use, Blood Pressure, Denervation, Hypertension, Hypertension/drug therapy, Kidney, Kidney/physiology, Kidney/surgery

Plain language summary

Renal denervation for improving outcomes in individuals with resistant hypertension

Key messages:

We don’t know if using renal denervation can improve risks to the heart, blood vessels and kidneys in people with resistant hypertension.

However, renal denervation might be effective in lowering blood pressure in people with resistant hypertension.

What is resistant hypertension?

Resistant hypertension is a condition in which high blood pressure levels continue even after several blood pressure‐lowering (antihypertensive) medicines have been given at high doses. It is estimated that 10% to 20% of people with hypertension have resistant hypertension.

What did we want to find out?

Renal denervation is a treatment that involves destroying renal nerves through a minimally invasive catheter‐based technique to treat high blood pressure. We wanted to know if renal denervation would safely reduce blood pressure and improve quality of life in people with resistant hypertension.

What did we do?

We searched for studies that compared renal denervation to other treatments or no treatment for who have resistant hypertension.

What did we find?

We found 15 studies that involved over 1400 people with resistant hypertension and lasted from 3 to 24 months.

Main results:

So far, we don’t know if using renal denervation can improve risks to the heart, blood vessels and kidneys in people with resistant hypertension. On the other hand, renal denervation might be effective in lowering blood pressure in people with resistant hypertension.

What are the main limitations of the evidence?

More studies that look at factors important to patients such as quality of life are needed. Studies that last longer and have more participants are needed to find out if denervation can lower blood pressure.

How up to date is the evidence?

The review updates our previous review. The evidence is up to date to November 2020

Summary of findings

Summary of findings 1. Summary of findings.

Renal denervation versus sham denervation or standard treatment
Patient or population: people with resistant hypertension Setting: outpatient  Intervention: renal denervation Comparison: sham procedure or standard treatment
Outcomes	*Illustrative comparative risks (95% CI)**		Effect estimate (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)
	Assumed risk	Corresponding risk
	Sham denervation/ Standard treatment	Renal denervation
Myocardial infarction	14 per 1000	18 per 1000 (6 to 54)	RR 1.31 (0.45 to 3.84)	742 (4 studies)	⊕⊕⊝⊝ low^1,2
Ischaemic stroke	14 per 1000	14 per 1000 (4 to 41)	RR 0.98 (0.33 to 2.95)	892 (5 studies)	⊕⊕⊝⊝ low^1,2
Unstable angina	22 per 1000	11 per 1000 (2 to 63)	RR 0.51 (0.09 to 2.89)	270 (3 studies)	⊕⊕⊝⊝ low^1,2
Hospitalisation	28 per 1000	35 per 1000 (14 to 87)	RR 1.24 (0.50 to 3.11)	743 (3 studies)	⊕⊕⊝⊝ low^1,2
Systolic 24‐hour ABPM (mmHg)	The mean systolic 24‐hour ABPM ranged across control groups from 139 to 157.1	The mean systolic 24‐hour ABPM in the intervention groups was on average 5.29 lower (95%CI ‐10.46 to ‐0.13)		1045 (9 studies)	⊕⊕⊕⊝ moderate¹
Diastolic 24‐hour ABPM (mmHg)	The mean diastolic 24‐hour ABPM ranged across control groups from 80 to 89.3	The mean diastolic 24‐hour ABPM in the intervention groups was on average 3.75 lower (95%CI ‐7.10 to ‐0.39)		1004 (8 studies)	⊕⊕⊕⊝ moderate¹
Systolic office BP (mmHg)	The mean systolic office BP ranged across control groups from 140 to 165.7	The mean systolic office BP in the intervention groups was on average 5.92 lower (95%CI ‐12.94 to 1.10)		1090 (9 studies)	⊕⊕⊕⊝ moderate¹
Diastolic office BP (mmHg)	The mean diastolic office BP ranged across control groups from 83.8 to 99.2	The mean diastolic office BP in the intervention groups was on average 4.61 lower (95%CI ‐8.23 to 0.99)		1049 (8 studies)	⊕⊕⊕⊝ moderate¹
eGFR or creatinine clearance (mL/min/1.73m²)	The mean eGFR or creatinine clearance ranged across control groups from 70.59 to 92.4	The mean eGFR or creatinine clearance in the intervention groups was on average 2.56 lower (95%CI ‐7.53 to 2.42)		822 (6 studies)	⊕⊕⊕⊝ moderate¹
Serum creatinine (mg/dL)	The mean serum creatinine ranged across control groups from 0.86 to 1.07	The mean serum creatinine in the intervention groups was on average 0.03 higher (95%CI ‐0.06 to 0.13)		721 (5 studies)	⊕⊕⊕⊝ moderate¹

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*The assumed risk is the observed risk in the reference (control) group. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

Legend ^{ABPM: ambulatory blood pressure monitoring BP: blood pressure CI: confidence interval CV: cardiovascular eGFR: estimated glomerular filtration rate MD: mean difference NA: information not available (data sparse or absent) RR: risk ratio}.

1. Downgraded 1 level for serious imprecision: Wide confidence intervals

2. Downgraded 1 level because outcome reported by less than half of the studies

Background

Description of the condition

Resistant or refractory hypertension (RH) is characterised by blood pressure levels persistently above target, in spite of the concurrent use of three antihypertensive agents of different classes at best‐tolerated doses, including a diuretic (Calhoun 2008). Data from cross‐sectional and hypertension outcome studies suggest that this condition is not infrequent, with an estimated prevalence of 10% to 20% in the general hypertensive population (Myat 2012). Individuals with resistant hypertension are 50% more likely to experience poor outcomes and adverse cardiovascular events than those with controlled hypertension (Judd 2014). The lack of efficacy of multiple interventions in addition to pharmacological therapy, including dietary and lifestyle modifications, emphasises the importance of finding new effective and safe treatments for treating this condition.

Description of the intervention

Renal sympathetic denervation comprises the ablation of renal afferent and efferent nerves through a minimally invasive, catheter‐based percutaneous intervention performed via femoral access. This is achieved by a thermal increase generated by the application of low‐dose radiofrequency or focussed ultrasound energy that is effective in disrupting large portions of nervous fibres located within the adventitia of the renal artery. Alternative ways to ablate renal nerves, including the administration of neurotoxic agents, cryotherapy or brachytherapy are currently under investigation.

How the intervention might work

Sympathetic hyperactivity has long been acknowledged as a major player in the genesis of resistant hypertension (Huan 2013). In studies conducted in the eighties, surgical sympathectomy was effective in some individuals in lowering blood pressure and symptoms associated with severe hypertension. However, this procedure is no longer used because of considerable side effects (Leong 2014). As with sympathectomy, renal denervation might improve blood pressure control by reducing abnormal renal adrenergic nerve activity. Furthermore, since other conditions, such as congestive heart failure, atrial fibrillation, sleep breathing disorders, and diabetes mellitus are all associated with an overactive sympathetic drive, this procedure might result in pleiotropic benefits, including improvements in glycaemic levels, sleep apnoea, arrhythmias, and oxidative stress (Witkowski 2011). Of note, in spontaneously hypertensive rats, renal denervation was able to ameliorate metabolic control and to prevent hypertensive stroke and brain injury, in addition to controlling blood pressure (Nakagawa 2013a; Nakagawa 2013b).

Why it is important to do this review

As shown in a milestone meta‐analysis, renal denervation reduced mean blood pressure at six months in individuals with persistent hypertension; intra‐procedural complications, including renal artery dissection and femoral pseudoaneurysms, were rare (Davis 2013). Unfortunately, data were mostly derived from observational, uncontrolled studies with limited follow‐up, small sample sizes, and high heterogeneity in blood pressure measurement. Since then, randomised controlled trials (RCTs) (INSPIRED; Warchol 2014) evaluated the effectiveness of this procedure in treating RH with variable results. In more recent meta‐analyses including RCTs, renal denervation did not produce significant benefit on blood pressure control in individuals with persistent hypertension (Fadl Elmula 2017, Agasthi 2019). Whether BP control really benefits from renal denervation, and whether this procedure might impact hard outcomes, such as mortality and cardiovascular events, remains unknown at this time. Over the past year, new evidence, based on larger RCTs and long‐term data on the efficacy of renal denervation on surrogate and hard end points, is now accruing, showing promising results. Therefore, an updated assessment of the efficacy and safety profile of this procedure is mandatory to define whether the benefits of implementing renal denervation in the clinical management of individuals with resistant hypertension outweigh the harms.

Objectives

To evaluate the short‐ and long‐term effects of renal sympathetic denervation in individuals with resistant hypertension on:

patient‐centred end points, including cardiovascular morbidity and mortality, all‐cause mortality, hospital admissions, and quality of life;
blood pressure control;
cardiovascular and metabolic profile;
kidney function;
adverse events, including but not limited to bradycardia, hypotension episodes, femoral artery pseudoaneurysm, and renal artery dissection.

Methods

Criteria for considering studies for this review

Types of studies

All RCTs and quasi‐RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth, or other predictable methods) of individuals with resistant hypertension undergoing renal sympathetic denervation procedures, without duration or language restrictions.

Types of participants

Adults (older than 18 years), with refractory or resistant hypertension, defined by the presence of a clinic blood pressure above target (higher than 140/90 mmHg, or higher than 130/80 mmHg in individuals with type 2 diabetes mellitus), despite the concomitant use of three or more antihypertensive drugs of different classes, including a diuretic.

Types of interventions

Any transcatheter renal sympathetic denervation procedures performed using contemporary percutaneous catheters compared with standard medical therapy or sham intervention.

Types of outcome measures

We considered a set of primary and secondary outcomes, according to clinical importance:

Primary outcomes

Fatal and non‐fatal cardiovascular events, including but not limited to myocardial infarction, cerebrovascular accidents, and congestive heart failure
All‐cause mortality
Any hospitalisation and duration of hospital stay (if long‐term data are available)
Quality of life (assessed using validated scales or any other instrument as reported by authors, such as the Short‐Form Health Survey (SF‐36)

Secondary outcomes

Blood pressure control (change in ABPM and clinic systolic, diastolic, and mean blood pressure)
Left ventricular hypertrophy
Atrial fibrillation episodes
Obstructive sleep apnoea severity (apnoea‐hypopnoea index)
Kidney function (change in serum creatinine, glomerular filtration rate (GFR), proteinuria or albuminuria, need for renal replacement therapy)
Metabolic profile (change in lipid and blood glucose levels and insulin resistance indices)
Withdrawal due to adverse effects, including but not limited to bradycardia and hypotensive episodes, femoral artery pseudoaneurysm, renal artery dissection, transient dizziness, pitting oedema, flank pain, and anaemia

Search methods for identification of studies

Electronic searches

For this updated review, the Cochrane Hypertension Information Specialist conducted systematic searches in the following databases for randomised controlled trials without language, publication year or publication status restrictions:

the Cochrane Hypertension Specialised Register via the Cochrane Register of Studies (to 3 November 2020);
the Cochrane Central Register of Controlled Trials (Issue 10, 2020) via Cochrane Register of Studies (to 3 November 2020);
Ovid MEDLINE(R) and Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Daily and Versions(R) (to 2 November 2020);
Ovid Embase (to 2 November 2020);
US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov ClinicalTrials.gov (www.clinicaltrials.gov) (to 3 November 2020);
World Health Organization International Clinical Trials Registry Platform (via CENTRAL) (to 3 November 2020).

The Information Specialist modelled subject strategies for databases on the search strategy designed for MEDLINE. Where appropriate, they were combined with subject strategy adaptations of the highly sensitive search strategy designed by Cochrane for identifying randomised controlled (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, Box 6.4.b. (Higgins 2011). Search strategies for major databases are provided in Appendix 1.

Searching other resources

The Cochrane Hypertension Information Specialist searched the Hypertension Specialised Register segment (which includes searches of MEDLINE and Epistemonikos for systematic reviews) to retrieve existing systematic reviews relevant to this systematic review, so that we could scan their reference lists for additional trials.
We checked the bibliographies of included studies and any relevant systematic reviews identified for further references to relevant trials.
Where necessary, we contacted authors of key papers and abstracts to request additional information about their trials.
We did not perform a separate search for adverse effects of interventions used for the treatment of hypertension. We considered adverse effects described in included studies only.
We checked the reference lists of cardiology and nephrology textbooks for additional resources.

Data collection and analysis

Selection of studies

Two authors (AL and LFI) independently screened titles and abstracts, and retained studies and reviews that might include relevant data or information on trials for review in detail; studies that were not applicable were excluded. The same authors (AL and LFI) independently assessed retrieved abstracts and, if necessary, the full text of these studies to determine which studies satisfied the inclusion criteria.

Data extraction and management

Two authors (AL and LFI) independently carried out data extraction using a standard electronic data extraction form. We arranged for translations of studies reported in non‐English language journals before assessment. If more than one publication of a study existed, we grouped the reports together and used the publication with the most complete data in the analyses. If relevant outcomes were published only in earlier versions of the study, we used such data.

Assessment of risk of bias in included studies

Two authors (AL and LFI) independently assessed the following items using the risk of bias assessment tool (Higgins 2011), which contained the following domains:

Sequence generation (selection bias);
Allocation concealment (selection bias);
Blinding:
- Participants and personnel (performance bias)
- Outcome assessors (detection bias);
Completeness of outcome data (attrition bias);
Selective outcome reporting (reporting bias);
Other sources of bias: e.g. funding bias.

Measures of treatment effect

We expressed dichotomous outcome results as risk ratios (RRs) with 95% confidence intervals (CIs). Where continuous scales of measurement were used to assess the effects of treatment, we reported results as mean differences (MDs) or standardised mean differences (SMDs) if different scales were reported, with 95% CI.

Unit of analysis issues

We appraised unit of analysis issues according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). For studies with more than two arms, we included only arms that met the inclusion criteria of the review. There were no further unit of analysis issues as no‐cluster RCTs or crossover studies have been found.

Dealing with missing data

We requested additional information from the corresponding author(s) by email. We carefully evaluated important data, such as numbers of screened and randomised participants, as well as numbers of intention‐to‐treat, as‐treated, and per‐protocol populations. We explored attrition in the study, such as dropouts, losses to follow‐up, and withdrawals. We appraised issues of missing data and imputation methods (such as last‐observation‐carried‐forward) according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Assessment of heterogeneity

We tested heterogeneity with a Chi² test on n ‐ 1 degrees of freedom, using an alpha of 0.05 for statistical significance, and used the I² statistic (Higgins 2003). We considered I² values of 25%, 50%, and 75% to correspond to low, medium, and high levels of heterogeneity.

Assessment of reporting biases

Where possible, we had planned to construct funnel plots to assess for the potential existence of small study bias (Higgins 2011).

Data synthesis

We analysed data for each outcome using Review Manager Web (RevMan 2014) in an attempt to estimate the overall effect. Data were pooled using random‐effects meta‐analysis, but the fixed‐effect model was also analysed to ensure robustness of the model chosen and susceptibility to outliers.

Subgroup analysis and investigation of heterogeneity

We had planned subgroup analyses to explore possible sources of heterogeneity including:

participants (age, race)
type of intervention (type of catheter employed and technique used)
type of comparator (standard therapy, sham, other denervation procedure)
presence/absence of diabetes
presence/absence of CV disease
severity of renal function impairment
duration and severity of hypertension (number and dosage of antihypertensive drugs used)

We had also planned an exploration of the effect of short‐ and long‐term follow‐up as a source of significant heterogeneity between studies.

However, due to the few number of studies eventually included, the majority of these subgroup analyses was not feasible.

Sensitivity analysis

We had planned sensitivity analyses to explore the influence of the following factors on the effect size:

repeating the analysis excluding any large studies, to establish how much they impacted on the results;
repeating the analysis taking into account the risk of bias;
repeating the analysis excluding unpublished studies.

Summary of findings and assessment of the certainty of the evidence

We had planned to construct a summary table via the GRADEpro‐GDT(GRADEpro GDT 2015), reporting:

a summary of findings from all the primary outcomes and a summary of findings from some secondary outcomes, that have been pre‐selected according to their clinical importance. These included cardiovascular outcomes (myocardial infarction, ischaemic stroke, unstable angina), hospital admission, blood pressure outcomes (24 h‐ABPM and office blood pressure) and renal function (serum creatinine and eGFR).
the certainty of the body of evidence supporting each of these outcomes using the GRADE approach (GRADEpro GDT 2015).

Results

Description of studies

The literature search is current to 3 November 2020.

Results of the search

The search identified 2749 records; we also identified five more records from additional searches or handsearches. Full‐text assessment of 259 records for this updated review resulted in the inclusion of 15 eligible studies (88 articles), comprising a total of 1416 participants (DENER‐HTN 2015; DENERVHTA; Desch 2015; Franzen 2012; HTN‐JAPAN 2015; INSPIRED; Moiseeva 2020‐B; Oslo RDN 2014; Prague‐15; RELIEF 2012; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; Warchol 2014), and 25 ongoing trials (27 articles; ALLEGRO‐HTN; DEPART; EnligHTN IV; ENSURE; KPS; NCT01848275; NCT01918111; NCT01968785; NCT02021019; NCT02346045; NCT02444442; NCT02608632; NCT02900729; NTR3444; PaCE; RADIANCE‐HTN; RAPID II; RDNP‐2012‐01; RENO; RENSYMPIS; ReSET‐2; RSD4CKD; RSDARH; RSDforAF; SYMPLICITY HTN‐4). We contacted the authors of some of the included studies for additional information about study methods and unreported data; five investigators responded to our queries (DENER‐HTN 2015; Moiseeva 2020‐B; Oslo RDN 2014; Prague‐15; SYMPLICITY HTN‐2 2010). Figure 1 depicts the flow of study selection.

Included studies

All fifteen included studies were parallel‐group RCTs with adult participants (Characteristics of included studies). Study duration ranged from three to 24 months. All studies except ReSET 2015, SYMPATHY, and Warchol 2014 excluded patients with estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m². The renal sympathetic denervation procedure was performed with the electrode radiofrequency Symplicity catheter system in 11 studies (DENER‐HTN 2015; DENERVHTA; Desch 2015; HTN‐JAPAN 2015; Moiseeva 2020‐B; Oslo RDN 2014; Prague‐15; ReSET 2015; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; Warchol 2014). Ablation was performed with an off‐the‐shelf saline‐irrigated radiofrequency catheter in RELIEF 2012. In INSPIRED and SYMPATHY, ablation was made with the EnligHTN™ multi‐electrode denervation system. In Franzen 2012, details of the denervation procedure were not provided. In seven studies, a series of four to six ablations per renal artery was performed (DENER‐HTN 2015; DENERVHTA; Desch 2015; HTN‐JAPAN 2015; Prague‐15; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014). Four ablations simultaneously were delivered at the mid/distal segment of the renal artery by INSPIRED and SYMPATHY. In Oslo RDN 2014, an average of eight (range 6 to 11) radiofrequency ablations were applied per renal artery. The number of ablations was not reported in five studies (Franzen 2012; Moiseeva 2020‐B; RELIEF 2012; ReSET 2015; Warchol 2014). In four studies, renal denervation was compared to sham procedure (Desch 2015; RELIEF 2012; ReSET 2015; SYMPLICITY HTN‐3 2014). Franzen 2012, HTN‐JAPAN 2015, INSPIRED, SYMPLICITY HTN‐2 2010, SYMPATHY, and Warchol 2014 compared renal denervation plus antihypertensive medications with antihypertensive medications alone. In five studies, the effects of renal denervation plus standard antihypertensive therapy were tested against an intensified pharmacological regimen (DENER‐HTN 2015; DENERVHTA; Moiseeva 2020‐B, Oslo RDN 2014; Prague‐15). One trial (Moiseeva 2020‐M; Moiseeva 2020‐B) randomly divided subjects into three equal groups according to the supplementation to the previously administered medication (M‐group, B‐group, D‐group). Outcomes available from studies were: incidence of myocardial infarction (DENER‐HTN 2015; Oslo RDN 2014; Prague‐15; SYMPLICITY HTN‐3 2014), ischaemic stroke (DENER‐HTN 2015; Prague‐15; ReSET 2015; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014), unstable angina (Prague‐15; ReSET 2015; SYMPLICITY HTN‐2 2010), all‐cause‐mortality and hospitalisations (Prague‐15; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐3 2014), quality of life (self‐reported health status)( INSPIRED), 24‐hour ambulatory blood pressure monitoring (ABPM) (DENER‐HTN 2015; DENERVHTA; Desch 2015; HTN‐JAPAN 2015; INSPIRED; Moiseeva 2020‐B; Moiseeva 2020‐M; Oslo RDN 2014; Prague‐15; RELIEF 2012; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐3 2014; Warchol 2014), daytime and/or night‐time ABPM (DENERVHTA; INSPIRED; Oslo RDN 2014; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐3 2014; Warchol 2014), office BP (DENER‐HTN 2015; DENERVHTA; HTN‐JAPAN 2015; INSPIRED; Moiseeva 2020‐B; Moiseeva 2020‐M; Oslo RDN 2014; Prague‐15; RELIEF 2012; SYMPATHY; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; Warchol 2014), home BP (DENER‐HTN 2015; HTN‐JAPAN 2015), left ventricular hypertrophy (DENERVHTA; Prague‐15; ReSET 2015; Warchol 2014) and kidney function (serum creatinine, eGFR) (DENER‐HTN 2015; DENERVHTA; HTN‐JAPAN 2015; INSPIRED; Oslo RDN 2014; Prague‐15; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; Warchol 2014), glucose metabolism measures (Prague‐15; Warchol 2014). Only Warchol 2014 reported on obstructive sleep apnea (OSA) severity. In addition, DENER‐HTN 2015; DENERVHTA; Desch 2015; HTN‐JAPAN 2015; INSPIRED; Oslo RDN 2014; Prague‐15; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; and Warchol 2014 looked systematically at the incidence of adverse effects associated to the procedure.

Excluded studies

We excluded 1056 records, 912 of which were excluded at title and abstract screening (Figure 1). One hundred and forty‐four records were excluded after full‐text evaluation. Reasons for exclusion were: inappropriate population, problem, or both (294 reports); inappropriate intervention, outcome, or both (463 reports); not an RCT (48 reports); editorial, comment, letter or review articles without reporting randomised trial data (251 reports). See Characteristics of excluded studies.

Risk of bias in included studies

We have shown summaries of the risks of bias in the included studies in Figure 2 and Figure 3.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

The overall risk of selection bias was highly variable. Random sequence generation was detailed in seven studies with a low risk of bias (DENER‐HTN 2015; DENERVHTA; Desch 2015; INSPIRED; Oslo RDN 2014; ReSET 2015; SYMPATHY), while there were insufficient data to inform assessment in the remainder. Only two of the included studies adequately described the allocation concealment methodologies that were applied (Oslo RDN 2014; SYMPLICITY HTN‐2 2010); this information was not stated in the remainder.

Blinding

The risk of performance and detection bias was also variable. Eight studies were fully open‐label, thus allowing a high risk of both biases (DENERVHTA; HTN‐JAPAN 2015; INSPIRED; Oslo RDN 2014; Prague‐15; SYMPATHY; SYMPLICITY HTN‐2 2010; Warchol 2014). DENER‐HTN 2015 was an open‐label trial but outcome assessors were blinded to the procedure. ReSET 2015 was double‐blinded; participants and personnel were unaware of treatment arm, while blinding of outcome assessment was not stated. In Desch 2015 and SYMPLICITY HTN‐3 2014, participants and outcome assessors were blinded to the treatment. In RELIEF 2012, patients were blinded to renal denervation or sham procedure, while outcome assessor blinding was unclear. In Franzen 2012 and Moiseeva 2020‐B, no overall information on blinding was specified.

Incomplete outcome data

The overall dropout rate ranged from 3% to 37% with no differences among groups, with the exception of DENER‐HTN 2015, INSPIRED and SYMPLICITY HTN‐3 2014, in which dropouts were more prevalent in the treatment arm, and in Prague‐15, in which 31 participants (62%) dropped out from the control group. Three studies reported no dropouts (HTN‐JAPAN 2015; Oslo RDN 2014; ReSET 2015). The information provided on attrition bias was insufficient to permit assessment in three studies (Franzen 2012; Moiseeva 2020‐B; RELIEF 2012). Seven studies were analysed on an intention‐to‐treat basis (DENER‐HTN 2015; DENERVHTA; HTN‐JAPAN 2015; Oslo RDN 2014; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐3 2014). In INSPIRED and SYMPLICITY HTN‐2 2010, analyses were performed on a per‐protocol basis. In Desch 2015 and Prague‐15, results were analysed on both a per‐protocol and intention‐to‐treat basis.

Selective reporting

All the predefined outcomes were reported in 11 studies (DENER‐HTN 2015; DENERVHTA; Desch 2015; HTN‐JAPAN 2015; INSPIRED; Moiseeva 2020‐B; Oslo RDN 2014; Prague‐15; SYMPATHY; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014). Some prespecified outcomes were not reported in RELIEF 2012 (office BP, serum creatinine) or in ReSET 2015 (daytime and night‐time BP, dipping status, diastolic and systolic ventricular function, left ventricular hypertrophy, renal sodium excretion, pulse wave velocity, a 25% or more decline in eGFR). Possible selective reporting was unclear in the remainder.

Other potential sources of bias

Seven studies declared funding from industry (DENER‐HTN 2015; DENERVHTA; HTN‐JAPAN 2015; Oslo RDN 2014; SYMPATHY; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014). In DENER‐HTN 2015 and DENERVHTA, the authors stated that the sponsor had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. In Oslo RDN 2014, the involvement of industry was unclear. In HTN‐JAPAN 2015, SYMPLICITY HTN‐2 2010, and SYMPLICITY HTN‐3 2014, the authors declared that data were monitored, collected, and managed by the sponsor. In SYMPATHY, an author received personal fees from Medtronic during the conduct of the study. No other sources of apparent bias were noticed in the other studies.

Effects of interventions

See: Table 1

The main effects of renal denervation on the primary outcomes and on the most important secondary outcomes are summarised in Table 1.

Primary outcomes

Non‐fatal cardiovascular events

In a meta‐analysis of four studies (742 participants), renal denervation may have little or no effect on the risk of myocardial infarction compared to sham or standard treatment (RR 1.31, 95% CI 0.45 to 3.84; Analysis 1.1); there was no heterogeneity (Chi² = 0.79; P = 0.85; I² = 0%; DENER‐HTN 2015; Oslo RDN 2014; Prague‐15; SYMPLICITY HTN‐3 2014). In data pooled from five studies (892 participants), renal denervation may have little or no effect on the risk of ischaemic stroke compared to no treatment (RR 0.98, 95% CI 0.33 to 2.95; Analysis 1.2); there was no heterogeneity (Chi² = 1.86; P = 0.76; I² = 0%; DENER‐HTN 2015; Prague‐15; ReSET 2015; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014). In a meta‐analysis of three studies (270 participants), renal denervation may have little or no effect on the risk of unstable angina compared to sham or standard therapy (RR 0.51, 95% CI 0.09 to 2.89; Analysis 1.3); there was no heterogeneity (Chi² = 0.0.44; P = 0.80; I² = 0%; Prague‐15; ReSET 2015; SYMPLICITY HTN‐2 2010).

1.1 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 1: Myocardial infarction

1.2 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 2: Ischaemic stroke

1.3 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 3: Unstable angina

All‐cause mortality

Data on all‐cause mortality were provided by two studies; in SYMPLICITY HTN‐3 2014, two patients in the renal denervation group and one in the sham group died. No deaths were recorded by Prague‐15 during the 24‐month follow‐up.

Hospitalisation

Data on hospitalisation were reported by three studies. In a meta‐analysis of three studies (743 participants), renal denervation may have little or no effect on the risk of hospitalisation compared to sham or standard treatment (RR 1.24, 95% CI 0.50 to 3.11; Analysis 1.4); there was no heterogeneity (Chi² = 1.00; P = 0.61; I² = 0%; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐3 2014).

1.4 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 4: Hospital admission

SYMPLICITY HTN‐3 2014 recorded hospital admissions for atrial fibrillation episodes and for new‐onset of heart failure; otherwise, in ReSET 2015 and SYMPATHY, patients required hospitalisation to adjust antihypertensive medication.

Quality of life

Data on quality of life (self‐reported health status) were only available in INSPIRED. After six‐month follow‐up, the self‐reported health status was 53.8 ± 22.3 in the control group and 75.0 ± 14.1 (baseline‐adjusted between‐group difference: 13.6 ;95% CI ‐7.4 to 34.6; P = 0.28).

Secondary outcomes

24‐hour ambulatory blood pressure monitoring (ABPM)

Twenty‐four hour ABPM was measured in 13 studies (DENER‐HTN 2015; DENERVHTA; Desch 2015; HTN‐JAPAN 2015; INSPIRED; (Moiseeva 2020‐B; Moiseeva 2020‐M); Oslo RDN 2014; Prague‐15; RELIEF 2012; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐3 2014; Warchol 2014). In a meta‐analysis of nine studies (10 subgroups) (1045 participants) (DENER‐HTN 2015; HTN‐JAPAN 2015; INSPIRED; Moiseeva 2020‐B; Moiseeva 2020‐M; Oslo RDN 2014; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐3 2014; Warchol 2014), renal denervation may reduce systolic 24‐hour ABPM when compared with sham or standard therapy (MD ‐5.29 mmHg, 95% CI ‐10.46 to ‐0.13; Analysis 1.5). The high heterogeneity found in this analysis (Chi² = 39.14; P < 0.0001; I² = 77%) was fully dependent on the type of radiofrequency system, multi‐electrode instead of a single electrode catheter (I² = 6%). In data pooled from eight studies (9 subgroups) (1004 participants) (DENER‐HTN 2015; INSPIRED; Moiseeva 2020‐B; Moiseeva 2020‐M; Oslo RDN 2014; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐3 2014; Warchol 2014), renal denervation may reduce diastolic 24‐hour ABPM as compared to sham or standard therapy (MD ‐3.75 mmHg, 95% CI ‐7.10 to ‐0.39; Analysis 1.6). There was high heterogeneity in this latter analysis (Chi² = 29.75, P = 0.0002; I² = 73%) that was reduced by selecting studies using different radiofrequency system (I² = 59%).

1.5 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 5: Systolic 24‐hour ABPM

1.6 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 6: Diastolic 24‐hour ABPM

In RELIEF 2012, the 24‐hour systolic/diastolic BP decreased by ‐17/‐12 mmHg (P = 0.006/P = 0.001) in the bilateral renal denervation group versus ‐5/‐5 mmHg (P = 0.22/P = 0.42) in the sham control group. In Prague‐15 , renal denervation (RD) and spironolactone addition (15 participants in both arms) showed a similar reduction in 24‐hour systolic/diastolic ABPM after 24‐month follow‐up (‐12.9/‐7.1 (RD) versus ‐13.9/‐7.0 mmHg (control). In DENERVHTA, spironolactone was superior to renal denervation (RDN) in reducing both 24‐hour SBP, ‐23.6 mmHg (‐31.9 to ‐15.3) versus ‐5.7 mmHg (‐14.8 to 3.4) and 24‐hour DBP, ‐10.2 (‐14.4 to ‐6.1) versus ‐3.7 (‐8.2 to 0.9), after six‐month follow‐up. HTN‐JAPAN 2015 recorded no difference between groups in 24‐hour diastolic BP (‐3.8 mmHg, 95% CI ‐8.3 to 0.6; P = 0.091). In Desch 2015, the mean change for the 24‐hour systolic BP was −7.0 mmHg (95% CI −10.8 to −3.2) for patients undergoing renal denervation and −3.5 mmHg (95% CI −6.7 to −0.2) in the sham group (P = 0.15), as analysed on an intention‐to‐treat basis. In the per‐protocol population, the change in 24‐hour systolic BP at six months was −8.3 mmHg (95% CI −11.7 to −5.0) for patients undergoing renal denervation and −3.5 mmHg (95% CI −6.8 to −0.2) in the sham group (P = 0.042). No changes in 24‐hour diastolic BP were recorded in either the intention‐to‐treat or per‐protocol analysis. All these single‐study data were directly retrieved from the correspondent papers.

Daytime ABPM

In separate meta‐analyses of five studies (234 participants), renal denervation may have no effect over standard treatment in reducing, respectively, systolic (MD 3.87 mmHg, 95% CI ‐5.02 to 12.76; I² = 70%; Analysis 1.7) and diastolic daytime ABMP (MD 2.93 mmHg, 95% CI ‐3.22 to 9.08; I² = 76%; Analysis 1.8) (DENERVHTA; INSPIRED; Oslo RDN 2014; SYMPATHY; Warchol 2014). Heterogeneity could not be further explored for the paucity of the studies included.

1.7 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 7: Systolic daytime ABPM

1.8 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 8: Diastolic daytime ABPM

In ReSET 2015, RD and sham groups had similar reductions at six months in daytime SBP and DBP compared, respectively, with baseline (SBP ‐6.1 ± 18.9 mmHg versus ‐4.3 ± 15.1 mmHg, P = 0.66; DBP ‐3.2 ± 10.8 versus ‐3.6 ± 8.3, P = 0.87).

Night‐time ABPM

In separate meta‐analyses of five studies (234 participants), renal denervation may have little or no effect on systolic (MD ‐1.65 mmHg, 95% CI ‐12.74 to 9.45; I² = 75%; Analysis 1.9) and diastolic night‐time ABPM (MD ‐1.08 mmHg, 95% CI ‐9.25 to 7.08; I² = 87%; Analysis 1.10) when compared with standard therapy (DENERVHTA; INSPIRED; SYMPATHY; Warchol 2014; Oslo RDN 2014). Heterogeneity could not be further explored for the paucity of the studies included.

1.9 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 9: Systolic night‐time ABPM

1.10 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 10: Diastolic night‐time ABPM

In ReSET 2015, after six‐month follow‐up, changes in night‐time SBP, (‐1.4 ± 18.2 mmHg (RD) versus ‐1.1 ± 14.4 mmHg (SHAM), P = 0.95) and DBP (‐0.6 ± 10.1 (RDN) versus ‐0.7 ± 8.8 (SHAM), P = 0.97) were very similar in both groups. In SYMPLICITY HTN‐3 2014, after six‐month follow‐up, the mean change in night‐time SBP was ‐6.1 ± 18.2 mmHg in the RDN group and ‐1.6 ± 19.7 mmHg in the sham group, P = 0.039 for RDN versus sham control during night‐time after Analysis of Covariance (ANCOVA) adjustment for baseline SBP.

Office BP

Office blood pressure (BP) was measured in 11 studies (DENER‐HTN 2015; DENERVHTA; HTN‐JAPAN 2015; INSPIRED; Moiseeva 2020‐B; Moiseeva 2020‐M; Oslo RDN 2014; Prague‐15; SYMPATHY; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; Warchol 2014). In a meta‐analysis of nine studies (10 subgroups) (1090 participants) (DENER‐HTN 2015; HTN‐JAPAN 2015; INSPIRED; Moiseeva 2020‐B; Moiseeva 2020‐M; Oslo RDN 2014; SYMPATHY; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; Warchol 2014), renal denervation had little or no effect on systolic office BP when compared with sham procedure or standard therapy (MD ‐5.92 mmHg, 95% CI ‐12.94 to 1.10; Analysis 1.11); there was high heterogeneity (Chi² = 64.48; P < 0.00001; I² = 86%). Performing subgroup analyses, benefits on systolic office BP became evident in studies using a multi‐electrode radiofrequency catheter (MD ‐5.10 mmHg, 95% CI ‐9.14 to ‐1.06) compared to in those using a single‐electrode catheter system, nullifying also the heterogeneity among studies (I² = 0%). In data pooled from eight studies (nine subgroups) (1049 participants) (DENER‐HTN 2015; INSPIRED; Moiseeva 2020‐B; Moiseeva 2020‐M; Oslo RDN 2014; SYMPATHY; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; Warchol 2014), renal denervation may reduce diastolic office BP when compared with sham or standard therapy (MD ‐4.61 mmHg, 95% CI ‐8.23 to ‐0.99; Analysis 1.12); there was high heterogeneity (Chi² = 34.20; P < 0.0001; I² = 77%) that was completely nullified after excluding studies performing ablations with a single‐electrode catheter system (I² = 0%).

1.11 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 11: Systolic office BP

1.12 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 12: Diastolic office BP

In DENERVHTA, spironolactone addition was more effective than RD in reducing office SBP, ‐29.4 (‐40.7 to ‐18.1) versus ‐17.5 (‐29.7 to ‐5.1) and DBP, ‐12.7 (‐20.0 to ‐5.5) versus ‐7.5 (‐15.5 to 0.5), respectively. Similarly, Prague‐15 showed better efficacy of spironolactone addition than RD in office BP reduction. At 24‐month follow‐up, office systolic/diastolic BP decreased by ‐19.9/‐9.2 mmHg (P = 0.007/P = 0.04) in the RD group versus ‐17.8/‐15.8 mmHg (P = 0.005/P < 0.001) in the spironolactone group. HTN‐JAPAN 2015 recorded a greater average diastolic office BP reduction in the renal denervation group than in the control group, with a change difference of ‐6.9 mmHg (95% CI ‐13.2 to 0.5; P = 0.036). These data were obtained from the correspondent study articles.

Home BP

In HTN‐JAPAN 2015, no change difference in home systolic and diastolic BP was observed between the renal denervation and control groups (‐5.6 mmHg (95% CI ‐14.5 to 3.2; P = 0.205) and ‐4.8 mmHg (95% CI ‐9.8 to 0.3; P = 0.065), respectively). In DENER‐HTN 2015, the mean change in home systolic and diastolic BP was ‐15.4 mmHg (95% CI ‐20.4 to ‐10.4) and ‐8.7 mmHg (95% CI ‐12.1 to ‐5.4) in patients undergoing renal denervation and ‐11.8 mmHg (95% CI ‐16.5 to ‐7.1) and ‐6.7 mmHg (95% CI‐9.8 to ‐3.5) in the control group, with no differences between groups (P = 0.30 and P = 0.37) for systolic and diastolic BP, respectively.

Left ventricular hypertrophy (LVH)

Data on left ventricular mass (LVM) and LVM indexed (LVMI) were provided by four studies (DENERVHTA; Prague‐15; ReSET 2015; Warchol 2014). In data pooled from two studies, renal denervation had little or no effect over sham or standard treatment on LVMI (MD ‐2.34, 95% CI ‐12.93 to 8.25; Analysis 1.13); there was no heterogeneity (Chi² = 0.02; P = 0.89; I² = 0%; ReSET 2015; Warchol 2014).

1.13 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 13: Left ventricular mass index (LVMI)

DENERVHTA recorded no differences in LVMI between RD (mean difference 1.83 g/m²; 95% CI −16.6 to 20.2) and spironolactone addition groups (mean difference −5.41 g/m²; 95% CI −23.0 to 12.2). Prague‐15 provided 24‐month follow‐up data on LVM and LVMI, reporting a reduction from baseline in the RD group (LVM mean difference ‐50 g [95% CI ‐83 to ‐17, P = 0.007; LVMI ‐10.5 g/m² 95% CI ‐17.3 to ‐3.8, P = 0.007]). No changes in LVM and LVMI were recorded in the control group.

Obstructive sleep apnoea (OSA) severity

Data on obstructive sleep apnoea (OSA) were only available in Warchol 2014. Three months after the procedure, the RDN group showed a decrease in OSA severity as evaluated by apnea hypopnea index (AHI) (from 39.4 ± 25.5 to 31.2 ± 23.4 events/hour; P = 0.015), whereas no difference from baseline in the control group (AHI, 31.6 ± 19.1 versus 30.4 ± 22.3 events/hours) were observed.

Kidney function

In a meta‐analysis of five studies (721 participants), renal denervation may result in little or no difference over sham or standard treatment on serum creatinine levels (MD 0.03 mg/dL, 95% CI ‐0.06 to 0.13; Analysis 1.14), with a moderate level of heterogeneity (Chi² = 12.63; P = 0.01; I² = 68%), which could not be further explored, as only five studies were included (INSPIRED; Oslo RDN 2014; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; Warchol 2014). Nevertheless, SYMPLICITY HTN‐3 2014 reported five cases in the renal denervation group and one case in the sham group, who had an increase in serum creatinine levels greater than 50% from baseline. One case of 50% increase in serum creatinine was also reported in the renal denervation group after six months of follow‐up in HTN‐JAPAN 2015.

1.14 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 14: Serum creatinine

In another meta‐analysis of six studies (822 participants), renal denervation had little or no effect on renal function, as estimated by eGFR or creatinine clearance, as compared to control (MD ‐2.56 mL/min, 95% CI ‐7.53 to 2.42; Analysis 1.15), with moderate heterogeneity (Chi² = 10.02, P = 0.07; I² = 50%), which could not be further explored (DENER‐HTN 2015; INSPIRED; Oslo RDN 2014; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; Warchol 2014).

1.15 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 15: eGFR/creatinine clearance

In Prague‐15, no change from baseline in serum creatinine and creatinine clearance was observed between the RD (SCr: mean difference 0.9 µmol/L (95% CI ‐7.3, 9.2; P = 0.81); CrCl ‐0.5 mL/s/1.73m² (95% CI ‐1.3, 0.3, P = 0.21) and control group (SCr 5.7 µmol/L (95% CI ‐0.4, 11.9; P = 0.06); CrCl ‐0.3 mL/s/1.73m² (95% CI ‐0.5, 0.01; P = 0.06), respectively.

DENERVHTA observed a greater renal function decline in the spironolactone with respect to RDN group; eGFR: mean difference ‐13.7 mL/min/1.73m² (95% CI ‐20.0 to ‐7.4) versus ‐3.0 (95% CI ‐9.8 to 3.9); SCr: 14.9 µmol/L (7.4 to 22.4) versus 5.9 (‐2.3 to 14.1). Otherwise, DENERVHTA recorded a decrease in UAE: −87.2 (95% CI −164.5 to −9.9) in the spironolactone compared with the RD group: −23.8 mg/g (95% CI −104.5 to 56.9), at six months.

Metabolic profile

Only Warchol 2014 reported information on glucose metabolism measures. After three months, there were no changes in fasting plasma glucose (RD, from 6.8 to 7.1 mmol/L; control group, from 6.7 to 6.7 mmol/L), insulin concentration (RD, from 13.4 to 12.8 mmol/L; control group, from 12.5 to 12.0 mmol/L) and glycosylated haemoglobin (RD, from 6.3 to 6.5%; control group, from 6.4 to 6.5%) in either group.

Adverse events

Major adverse events were systematically collected by 11 studies (DENER‐HTN 2015; DENERVHTA; HTN‐JAPAN 2015; INSPIRED; Oslo RDN 2014; Prague‐15; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; Warchol 2014). SYMPATHY registered 36 serious adverse events (n = 24, 26% in the intervention group and n = 12, 27% in the usual care group) and 17 periprocedural complications, including vascular (n = 4), bleeding (n = 8) and five other mild complications (back pain, groin pain and hypotension in the RD group. ReSET 2015 recorded minor symptoms, such as headache, atypical chest pain, muscle convulsions and fatigue in five RD and six SHAM patients, respectively. DENERVHTA observed that mild groin haematoma and transient symptomatic hypotension developed in five patients in the RD group; one patient in the spironolactone group reported hyponatraemia, muscle cramps, and transient symptomatic hypotension. HTN‐JAPAN 2015 and INSPIRED reported no periprocedural complications in either the RD or control arms. No study provided information on the occurrence of transient dizziness or anaemia.

Bradycardia

In a meta‐analysis of three studies (220 participants), renal denervation may increase the risk of bradycardia occurrence than other treatments (RR 6.63, 95% CI 1.19 to 36.84; Analysis 1.16), with no heterogeneity (Chi² = 0.63; P = 0.73; I² = 0%; Oslo RDN 2014; Prague‐15; SYMPLICITY HTN‐2 2010). Warchol 2014 observed five episodes of bradycardia in the whole study population.

1.16 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 16: Bradycardia

Femoral artery pseudoaneurysm

Pooled data from two studies (201 participants) showed that renal denervation may have little or no effect on the risk for femoral artery pseudoaneurysm compared to standard therapy (RR 3.96, 95% CI 0.44 to 35.22; Analysis 1.17), with no heterogeneity (Chi² = 0.04; P = 0.84; I² = 0%; Prague‐15; SYMPLICITY HTN‐2 2010). SYMPATHY observed two cases of spurious aneurysm in the RD group.

1.17 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 17: Femoral artery pseudoaneurysm

Renal artery dissection

In Prague‐15, there was one case of renal artery dissection related to the procedure.

Renal artery vasospasm

Four cases of renal artery vasospasm in patients undergoing renal denervation were observed in Prague‐15. Warchol 2014 reported one case of transient renal artery spasm which occurred after radiofrequency application.

New renal‐artery stenosis

SYMPLICITY HTN‐3 2014 reported one case of re‐stenosis in the renal denervation group (documented as new renal artery stenosis of more than 70%) within the six‐month follow‐up.

Flank pain

In a meta‐analysis of two studies (199 participants), renal denervation may have little or no effect on the risk of flank pain compared to control (RR 4.30, 95% CI 0.48 to 38.28; Analysis 1.18), with no heterogeneity (Chi² = 0.08; P = 0.78; I² = 0%; DENER‐HTN 2015; SYMPLICITY HTN‐2 2010).

1.18 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 18: Flank pain

Pitting oedema

One case of oedema requiring hospital admission was recorded in SYMPLICITY HTN‐2 2010.

Hypotensive episodes

In a meta‐analysis of three studies (143 participants), the renal denervation procedure had little or no effect on the risk of hypotensive episodes compared to no treatment (RR 1.60, 95% CI 0.20 to 12.63; Analysis 1.19); the analysis had moderate heterogeneity (Chi² = 4.77; P = 0.09; I² = 58%; Oslo RDN 2014; SYMPLICITY HTN‐2 2010; DENERVHTA).

1.19 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 19: Hypotensive episodes

Hypertensive crisis

In data pooled from three studies (722 participants), renal denervation had little or no effect on the risk of hypertensive episodes as compared with controls (RR 0.71, 95% CI 0.35 to 1.45; Analysis 1.20), with no heterogeneity (Chi² = 1.83; P = 0.40; I² = 0%; DENER‐HTN 2015; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014).

1.20 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 20: Hypertensive crisis

Hyperkalaemia

In a meta‐analysis of three studies (224 participants), the denervation procedure had little or no effect on the risk of hyperkalaemia compared to standard therapy (RR 0.43, 95% CI 0.05 to 3.89; Analysis 1.21). There was low heterogeneity in this analysis (Chi² = 3.17; P = 0.21; I² = 37%), which could not be further explored, as only three studies were included (DENER‐HTN 2015; DENERVHTA; Prague‐15).

1.21 — Comparison 1: Renal denervation vs. sham/standard therapy, Outcome 21: Hyperkalaemia

Syncope

In DENER‐HTN 2015, one patient in the control group experienced an episode of syncope. In DENERVHTA, no syncope occurred in either group.

Embolic events

In SYMPLICITY HTN‐3 2014, one case of embolic event resulting in end‐organ damage was reported in the renal denervation group.

Withdrawals

Twelve studies provided information on withdrawals (DENER‐HTN 2015; DENERVHTA; Desch 2015; HTN‐JAPAN 2015; INSPIRED; Oslo RDN 2014; Prague‐15; ReSET 2015; SYMPATHY; SYMPLICITY HTN‐2 2010; SYMPLICITY HTN‐3 2014; Warchol 2014). SYMPLICITY HTN‐3 2014 recorded 14 (3.8%) withdrawals from the renal denervation group and two (1.2%) from the control arm. In SYMPLICITY HTN‐2 2010, there were three withdrawals from both the intervention and control arms. DENER‐HTN 2015 reported five (10%) withdrawals from the renal denervation group. In Desch 2015, six participants (17%) withdrew from the renal denervation and two (5.55%) from the sham group. Prague‐15 recorded seven (13.7%) and 31 (62%) withdrawals from the renal denervation and control groups, respectively. Three studies reported no withdrawals (HTN‐JAPAN 2015; Oslo RDN 2014; ReSET 2015). SYMPATHY recorded eight withdrawals (5.8%) (five in the RDN and three in the usual care group).

Outcomes not stated

No RCT provided data on the following outcomes: fatal cardiovascular events, need for renal replacement therapy and proteinuria.

Sensitivity analyses, investigation of heterogeneity, and publication bias

Such investigations were not performed due to the small number of studies retrieved.

Discussion

Summary of main results

In patients with resistant hypertension, a renal denervation procedure may have little or no effect on the risk of major cardiovascular events, including myocardial infarction, ischaemic stroke, and unstable angina, as well as hospital admission, compared with controls. Nevertheless, this procedure may decrease 24‐hour ABPM and office diastolic blood pressure. Little or no effect was observed on renal function, while it likely increases the risk of bradycardia episodes. Renal denervation had little or no effect on the risk of other adverse effects, such as femoral artery pseudo‐aneurysm, flank pain, hypotensive or hypertensive episodes, and long‐term hyperkalaemia. Data on mortality and other adverse effects were limited to single studies.

Overall completeness and applicability of evidence

Our findings suggest that RD could be effective for blood pressure control and be safe, with a low complications and adverse events rate. Nevertheless, many clinically relevant outcomes, such as fatal cardiovascular events, quality of life, sleep apnoea severity, need for renal replacement therapy and metabolic profile, were absent or poorly explored in some included RCTs. Heterogeneity was high in the majority of analyses carried out, hampering the overall reliability of findings. Although exploration of heterogeneity was not feasible in the majority of analyses, due to the paucity of studies included, it can be speculated that differences among individual study designs (e.g. use of sham procedure or standard therapy as control, presence or absence of blinding in outcome assessment, use of multiple catheter systems) may represent one of the main causes underlying this phenomenon. In most trials, both study groups were simultaneously treated with optimal antihypertensive therapy to decrease blood pressure to an established target. Administration of these drugs was variable and non‐reproducible. Procedural methods were also heterogeneous among studies, particularly in terms of type of catheter employed, number of applications, energy delivered and target portion of the renal artery. Sakakura and colleagues recently observed that nervous fibres are mostly concentrated in the middle and proximal segments of the renal artery while their number decrease in the distal segment (Sakakura 2014). Previous data evidenced a maximum procedural efficacy after ablation in the whole circumference of the renal artery and a dose‐response dependency directly related to the amount of energy delivered (Kandzari 2015). The lack of standardised methods for renal denervation may hamper the reliability of comparisons among studies and, in some cases, even raise the question as to whether the procedure was truly successful (Esler 2015). Our results show a greater decrease in office and 24h ABPM among patients who underwent the multi‐electrode catheter denervation system, performing four ablations simultaneously delivered at the mid/distal segment of the renal artery, compared to the first generation procedures (radiofrequency ablation via single‐electrode catheter). Type of ablation therapy employed and target sites for ablation must be explored in future trials. The available evidence suggests that RD could be effective optimising the procedure by carefully selecting patients with truly resistant hypertension and applying new methods and technologies guided by a better understanding of renal nerve anatomy.

Quality of the evidence

The GRADE quality of the evidence (Guyatt 2008) was low for cardiovascular morbidity outcomes and adverse effects, moderate for blood pressure and renal function outcomes and low to very low for the remaining outcomes. The quality of evidence was mostly influenced by the imprecision of results (wide confidence intervals) or the low number of studies providing quantitative data on the same outcome, or both. Of note, although few studies were at high risk of bias for allocation concealment or blinding, in the majority of the included studies, the risk of bias remained unclear for most items, making it therefore difficult to evaluate the impact on the quality of evidence.

Potential biases in the review process

Points of strength of this review are represented by a peer‐reviewed protocol, a systematic search of electronic databases, and data extraction, analysis, and risk of bias assessment completed independently by two authors, according to current methodological standards. The main limitation is represented by the data obtainable from the included studies. Studies were mainly focussed on small populations and short treatment periods. As a result, most trials were not adequately powered to capture exhaustive information on hard, patient‐centred outcomes, such as fatal or non‐fatal cardiovascular events. Moreover, use of multiple catheter systems could potentially contribute to the heterogeneity observed in our analysis.

Agreements and disagreements with other studies or reviews

In a previous systematic review, renal denervation was apparently efficacious in reducing mean blood pressure at six months in individuals with resistant hypertension (RH) (Davis 2013). Unfortunately, this review was mostly based on data from observational, uncontrolled studies with limited follow‐up, small sample sizes and high heterogeneity in blood pressure measurement. Conversely, two of the most recent meta‐analyses (Fadl Elmula 2017 and Agasthi 2019) that included RCTs did not show any significant effect on blood pressure in patients with RH following renal denervation. The authors confirmed the lack of evidence supporting a widespread use of this procedure in clinical practice, advocating for future clinical trials with a longer observation time, sham control study design and novel renal denervation techniques. Over the past year, multiple randomised controlled trials evaluating the effect of RD on RH patients showed promising results (INSPIRED; Moiseeva 2020‐B; Moiseeva 2020‐M; Warchol 2014). Our meta‐analysis of high‐quality RCTs showed significant benefits of this procedure over sham/medical therapy in reducing 24‐hour ABPM and office diastolic blood pressure. Moreover, patients who underwent RD had no significant changes in renal function, supporting the safety profile of the procedure.

Authors' conclusions

Implications for practice.

The evidence accrued so far is insufficient to support the use of renal denervation as a clinically useful procedure for improving cardiovascular outcomes in patients with resistant hypertension. In contrast, a moderate‐quality body of evidence suggests that this procedure may result in a reduction in blood pressure levels, although it probably increases the risk of bradycardia episodes.

Implications for research.

Focussed trials, powered for patient‐centred instead of surrogate outcomes, with longer follow‐up periods, larger sample sizes, more standardised procedural methods and, possibly, examining particular subgroups of patients with resistant hypertension (e.g. subjects with different cardiovascular or renal risk profiles) are needed to clarify the optimal target population for this procedure. Study design providing a sham control procedure and blinded outcome assessors are indispensable for minimising bias and improving the reliability of findings. Results from ongoing trials testing alternative methods for performing renal nerve ablation, e.g. focussed ultrasounds, the administration of neurotoxic agents, cryotherapy or brachytherapy are also awaited.

What's new

Date	Event	Description
20 November 2021	New citation required and conclusions have changed	3 new studies incorporated. Conclusions changed.
16 January 2021	New search has been performed	Search findings were updated until 3 November 2020. The updated search identified three new trials.

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History

Protocol first published: Issue 1, 2015 Review first published: Issue 2, 2017

Acknowledgements

We thank Dr Murray Esler, Dr Michel Azizi, Dr Jan Rosa, Dr Sverre Erik Kjeldsen, Dr M. Fadl Elmula and Dr Anna Moiseeva for providing additional trial data. We would also like to thank the Cochrane Hypertension Group, particularly Mr Ciprian Jauca and Mr Douglas Salzwedel, for their valuable support, and the referees for their feedback and advice during the preparation of the review.

Appendices

Appendix 1. Search strategies

Database: Ovid MEDLINE(R) and Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Daily and Versions(R) <1946 to November 02, 2020> Search Date: 3 November 2020 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ 1 denervation/  2 *catheter ablation/  3 radiofrequency ablation/  4 ((kidney? or renal or transcatheter) adj6 (denervat$ or sympathectom$)).mp.  5 ((radiofrequency or radio frequency) adj2 (ablation? or catheter? or probe?)).tw,kf.  6 or/1‐5  7 hypertension/  8 essential hypertension/  9 (antihypertens$ or hypertens$).tw,kf.  10 ((elev$ or high$ or rais$) adj3 (arterial pressure or blood pressure or diastolic pressure or systolic pressure)).tw,kf. 11 ((elev$ or high$ or rais$) adj3 (bp or dbp or sbp)).tw,kf. 12 or/7‐11 13 randomized controlled trial.pt. 14 controlled clinical trial.pt. 15 randomized.ab.  16 placebo.ab.  17 dt.fs.  18 randomly.ab. 19 trial.ab. 20 groups.ab.  21 or/13‐20  22 animals/ not (humans/ and animals/) 23 21 not 22 24 6 and 12 and 23

‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

Database: Cochrane Hypertension Specialised Register via Cochrane Register of Studies

Search Date: 3 November 2020

‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ #1 MESH DESCRIPTOR Denervation AND INSEGMENT #2 denerva* AND INSEGMENT #3 catheter ablation* AND INSEGMENT #4 radiofrequency ablation* AND INSEGMENT #5 sympathectom* AND INSEGMENT #6 (#1 OR #2 OR #3 OR #4 OR #5) AND INSEGMENT #7 MESH DESCRIPTOR Hypertension AND INSEGMENT #8 MESH DESCRIPTOR Essential Hypertension AND INSEGMENT #9 hypertens* AND INSEGMENT #10 ((elevated OR high* OR rais*) NEAR3 blood pressure) AND INSEGMENT #11 (#7 OR #8 OR #9 OR #10) AND INSEGMENT #12 (CCT OR RCT):DE AND INSEGMENT #13 Review:ODE AND INSEGMENT #14 (#12 OR #13) AND INSEGMENT #15 #6 AND #14 AND INSEGMENT

Database: Cochrane Central Register of Controlled Trials (Issue 10, 2020) via Cochrane Register of Studies

Search Date: 3 November 2020 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ #1 MESH DESCRIPTOR Denervation AND CENTRAL:TARGET #2 denerva* AND CENTRAL:TARGET #3 catheter ablation* AND CENTRAL:TARGET #4 radiofrequency ablation* AND CENTRAL:TARGET #5 sympathectom* AND CENTRAL:TARGET #6 (#1 OR #2 OR #3 OR #4 OR #5) AND CENTRAL:TARGET #7 MESH DESCRIPTOR Hypertension AND CENTRAL:TARGET #8 MESH DESCRIPTOR Essential Hypertension AND CENTRAL:TARGET #9 hypertens* AND CENTRAL:TARGET #10 ((elevated OR high* OR rais*) NEAR3 blood pressure) AND CENTRAL:TARGET #11 (#7 OR #8 OR #9 OR #10) AND CENTRAL:TARGET #12 #6 AND #11 AND CENTRAL:TARGET

Database: Embase <1974 to 2020 November 02> Search Date: 3 November 2020 ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ 1 renal denervation/  2 *catheter ablation/  3 *radiofrequency ablation/  4 ((kidney? or renal or transcatheter) adj6 (denervat$ or sympathectom$)).tw.  5 ((radiofrequency or radio frequency) adj2 (ablation? or catheter? or probe?)).tw. 6 or/1‐5  7 exp hypertension/  8 hypertens$.tw.  9 ((elev$ or high$ or rais$) adj3 (arterial pressure or blood pressure or diastolic pressure or systolic pressure)).tw.  10 ((elev$ or high$ or rais$) adj3 (bp or dbp or sbp)).tw. 11 or/7‐10 12 randomized controlled trial/  13 controlled clinical trial/ 14 crossover procedure/ 15 double‐blind procedure/  16 (randomi?ed or randomly).tw.  17 (crossover$ or cross‐over$).tw.  18 placebo.ab. 19 (doubl$ adj blind$).tw.  20 assign$.ab.  21 allocat$.ab.  22 or/12‐21 23 (exp animal/ or animal.hw. or nonhuman/) not (exp human/ or human cell/ or (human or humans).ti.)  24 22 not 23 25 6 and 11 and 24

Database: ClinicalTrials.gov

Search Date: 3 November 2020

‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ Condition or disease: Hypertension Study type: Interventional Studies (Clinical Trials) Study Results: All Studies Intervention/treatment: denervation 

Data and analyses

Comparison 1. Renal denervation vs. sham/standard therapy.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Myocardial infarction	4	742	Risk Ratio (M‐H, Random, 95% CI)	1.31 [0.45, 3.84]
1.2 Ischaemic stroke	5	892	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.33, 2.95]
1.3 Unstable angina	3	270	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.09, 2.89]
1.4 Hospital admission	3	743	Risk Ratio (M‐H, Random, 95% CI)	1.24 [0.50, 3.11]
1.5 Systolic 24‐hour ABPM	10	1045	Mean Difference (IV, Random, 95% CI)	‐5.29 [‐10.46, ‐0.13]
1.6 Diastolic 24‐hour ABPM	9	1004	Mean Difference (IV, Random, 95% CI)	‐3.75 [‐7.10, ‐0.39]
1.7 Systolic daytime ABPM	5	234	Mean Difference (IV, Random, 95% CI)	3.87 [‐5.02, 12.76]
1.8 Diastolic daytime ABPM	5	234	Mean Difference (IV, Random, 95% CI)	2.93 [‐3.22, 9.08]
1.9 Systolic night‐time ABPM	5	234	Mean Difference (IV, Random, 95% CI)	‐1.65 [‐12.74, 9.45]
1.10 Diastolic night‐time ABPM	5	234	Mean Difference (IV, Random, 95% CI)	‐1.08 [‐9.25, 7.08]
1.11 Systolic office BP	10	1090	Mean Difference (IV, Random, 95% CI)	‐5.92 [‐12.94, 1.10]
1.12 Diastolic office BP	9	1049	Mean Difference (IV, Random, 95% CI)	‐4.61 [‐8.23, ‐0.99]
1.13 Left ventricular mass index (LVMI)	2	105	Mean Difference (IV, Random, 95% CI)	‐2.34 [‐12.93, 8.25]
1.14 Serum creatinine	5	721	Mean Difference (IV, Random, 95% CI)	0.03 [‐0.06, 0.13]
1.15 eGFR/creatinine clearance	6	822	Mean Difference (IV, Random, 95% CI)	‐2.56 [‐7.53, 2.42]
1.16 Bradycardia	3	220	Risk Ratio (M‐H, Random, 95% CI)	6.63 [1.19, 36.84]
1.17 Femoral artery pseudoaneurysm	2	201	Risk Ratio (M‐H, Random, 95% CI)	3.96 [0.44, 35.22]
1.18 Flank pain	2	199	Risk Ratio (M‐H, Random, 95% CI)	4.30 [0.48, 38.28]
1.19 Hypotensive episodes	3	143	Risk Ratio (M‐H, Random, 95% CI)	1.60 [0.20, 12.63]
1.20 Hypertensive crisis	3	722	Risk Ratio (M‐H, Random, 95% CI)	0.71 [0.35, 1.45]
1.21 Hyperkalaemia	3	224	Risk Ratio (M‐H, Random, 95% CI)	0.43 [0.05, 3.89]

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

DENER‐HTN 2015.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: France Setting: University
Participants	Number of patients randomised/analysed: 106/101 Age: range 18 to 75 years, mean 55.2 Males (%): 62.2 Office Blood Pressure (BP; mmHg): 158/93 Diabetes mellitus (%): 21.7 Hyperlipidaemia (%): 46.2 Prior cardiovascular event (%): 25.5 Prior stroke (%): 10.4 Obstructive sleep apnoea (%): 27.4 eGFR (mL/min/1.73 m²): 89 Antihypertensive treatment: Diuretics (%): 100 ACEIs (%): 84 ARBs (%): 16 CCBs (%): 94.3 Exclusion criteria: secondary hypertension, eGFR < 40 mL/min/1.73 m², history of severe cardiovascular disease or stroke in the previous three months, history of contraindication or intolerance to the study drugs, type 1 diabetes mellitus, brachial circumference > 42 cm, atrial fibrillation, unsuitable renal artery anatomy (accessory renal arteries > 3 mm in diameter, main renal artery < 4 mm in diameter or < 20 mm in length, renal artery stenosis > 30%, prior renal artery intervention or kidney length < 90 mm) ruled out by computed tomography angiogram, magnetic resonance angiogram or renal angiogram
Interventions	Treatment group: N = 48, renal denervation plus standardised stepped‐care antihypertensive treatment (SSAHT) Control group: N = 53, standardised stepped‐care antihypertensive treatment (SSAHT) alone Renal denervation procedure: Ablation done with the single electrode radiofrequency Symplicity catheter. A series of four to six ablations per renal artery were performed. SSAHT: Initial standardised triple therapy (indapamide 1.5 mg, ramipril 10 mg or irbesartan 300 mg, and amlodipine 10 mg daily) + spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day Follow‐up: up to 6 months
Outcomes	Daytime ambulatory blood pressure monitoring (ABPM) 24‐hour ABPM Office and home ABPM Proportion of patients with controlled blood pressure Estimated Glomerular Filtration Rate (eGFR) Adverse events
Notes	Modified intention‐to‐treat and per‐protocol analyses performed
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The randomisation sequence was generated by computer and stratified by centres using randomised blocks of small size and permutation of treatments within each block".
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinded outcome assessors
Incomplete outcome data (attrition bias) All outcomes	Low risk	5/48 (10%) dropouts in treatment group (three lost to follow‐up and two with missing ABPM). A modified intention‐to‐treat analysis was performed.
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	Low risk	The funder of the study (French Ministry of Health) had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

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DENERVHTA.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Spain Setting: Hospital
Participants	Number of patients randomised/analysed: 27/24 Age: 63 years Males (%): 62 24‐h ABPM (mmHg): 152/80 24‐h HR (bpm): 65 Daytime ABPM (mmHg): 155/83 Night‐time ABPM (mmHg): 143/75 Office BP (mmHg): 169/89 Serum creatinine (μmol/L): 84 Microalbuminuria (%): 45 eGFR (mL/min/1.73 m²): 80 DM type 2 (%): 49 Previous CVD (%): 21 Smokers (%): 38 Mean antihypertensive drugs: 4.1 Antihypertensive treatment: Diuretics (%): 100 RAS blockers (%): 100 CCBs (%): 80 β‐blockers (%): 66 α‐blockers (%): 47 Centrally acting drugs (%): 13 Exclusion criteria: pregnancy, secondary hypertension, eGFR < 45 mL/min/1.73 m², unsuitable anatomy of renal arteries (diameter < 4 mm and length < 20 mm) including significant (≥ 50%) renal arterial stenosis, renal artery stent, single functional kidney, previous nephrectomy, contrast agent allergy, hyperthyroidia. Treatment with an aldosterone receptor blocker (spironolactone, eplerenone), pre‐randomisation serum potassium (K⁺) level ≥ 5.5 mmol/L, significant renal vascular anomalies, significant valvular heart disease, major vascular event (myocardial infarction, unstable angina or cerebrovascular disease) < 6 months prior to study enrolment
Interventions	⦁ Treatment group: n = 11, RDN plus usual medical treatment  ⦁ Control group: n = 13, spironolactone (50 mg/day) plus usual medical treatment ⦁ Renal denervation procedure: radiofrequency Symplicity (Medtronic) catheter‐based therapy for renal denervation. Four‐to‐six low‐power radio frequency treatments along the length of both main renal arteries ⦁ Follow‐up: up to 6 months
Outcomes	24‐hour SBP Daytime and night‐time BP Office BP Blood pressure variability (BPV) Changes in renal function (eGFR, serum creatinine, UAE, serum potassium) Changes on markers of preclinical target organ damage (microalbuminuria, increased pulse wave velocity [PWV], left ventricular (LV) hypertrophy, and carotid plaques and/or increased wall thickness) Any adverse events
Notes	Intention‐to‐treat analysis done by last‐observation‐carried‐forward method
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization sequence was generated by computer and stratified by centres using randomized blocks of small size and permutation of treatments within each block".
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label
Incomplete outcome data (attrition bias) All outcomes	Low risk	3/27 (11.1%) dropouts (2 in RDN and 1 in spironolactone group); intention‐to‐treat analysis
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	Low risk	The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

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Desch 2015.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Germany Setting: University
Participants	Number of patients randomised/analysed (intention‐to‐treat, per‐protocol): 71/(67,63) Age: 60 years Males (%): 73 Daytime ABPM (mmHg): 144/82 Smokers (%): 14 History of stroke/transient ischaemic attack (%): 7 Coronary artery disease (%): 53 Peripheral arterial disease (%): 9 Diabetes mellitus (%): 45 eGFR (mL/min/1.73 m²): 82 Antihypertensive drugs (n): 4.4 ≥ 5 antihypertensive drugs (%): 40 Antihypertensive treatment: Diuretics (%): 96 ACEIs (%): 54 ARBs (%): 47 CCBs (%): 67 Direct renin inhibitors (%): 6 β‐blockers (%): 93 α‐blockers (%): 18 Aldosterone antagonists (%): 5 Exclusion criteria: mean daytime systolic BP on 24‐hour ABPM < 135 and > 149 mmHg or mean daytime diastolic BP < 90 and > 94 mmHg, unsuitable anatomy for renal denervation, severe renal artery stenosis, eGFR < 45 mL/min/1.73 m², change in BP medication in the 4 weeks preceding randomisation, unwillingness to adhere to unchanging BP medication during the study period of 6 months, unstable angina pectoris, myocardial infarction within 6 months prior to randomisation, planned surgery or cardiovascular intervention within 6 months after randomisation, severe heart valve disease, pregnancy, and severe comorbidities with limited life expectancy
Interventions	Treatment group: N = 35, renal denervation Control group: N = 36, sham procedure Renal denervation procedure: Ablation done with the Symplicity Flex catheter. Four to 6 ablation runs of 2 minutes for each renal artery were delivered circumferentially to the renal artery wall from distal to proximal. Sham procedure: Angiography of the renal arteries and a simulated renal denervation procedure with 4 to 6 sham runs for each renal artery guided by 2‐minute acoustic signals similar to those of the Symplicity generator Follow‐up: up to 6 months
Outcomes	24‐hour BP in the intention‐to‐treat population 24‐hour BP in the per‐protocol population Adverse events All‐cause death
Notes	Intention‐to‐treat and per‐protocol analyses performed
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were assigned to the treatment groups by simple randomisation, in a 1:1 ratio, via an internet‐based system using a computer‐generated list of random numbers".
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Single‐blind
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All investigators (including personnel responsible for BP assessment) were blinded to treatment assignment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	8/71 (11%) dropouts (6 in RD and 2 in sham procedure); intention‐to‐treat and per‐protocol analyses performed
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	Unclear risk	No apparent other sources of bias

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Franzen 2012.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Germany Setting: Hospital
Participants	Number of patients randomised/analysed: 27/27 Age: range 18 to 82 years, mean 63 Systolic BP (mmHg): > 150 Antihypertensive drugs (n): 4.7
Interventions	Treatment group: N = 21 Control group: N = 6 Follow‐up: up to 6 months
Outcomes	Peripheral systolic BP Central systolic BP Pulse wave velocity (PWV) Aortic stiffness parameters
Notes	Study in abstract version only. Unclear if patients were truly randomised (quote: "21 patients were randomised to PRD. 6 patients served as controls")
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not specified
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not specified
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not specified
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not specified
Selective reporting (reporting bias)	Unclear risk	Not specified
Other bias	Unclear risk	Not specified

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HTN‐JAPAN 2015.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Japan Setting: University and hospital
Participants	Number of patients randomised/analysed: 41/41 Age: range 20 to 80 years, mean: 58 Males (%): 76 Office systolic BP (mmHg): 180 24‐h mean systolic ABPM (mmHg): 164 Type 2 diabetes mellitus (%): 50 Hypercholesterolaemia (%): 32 Prior stroke (%): 17 Obstructive sleep apnoea (%): 10 eGFR (mL/min/1.73 m²): ≥ 45 Antihypertensive drugs (n): 4.9 Antihypertensive treatment: Diuretics (%): 100 ACEIs (%): 12 ARBs (%): 98 CCBs (%): 95 Direct renin inhibitors (%): 0 β‐blockers (%): 75 α‐blockers (%): 33 Aldosterone antagonist (%): 41 Exclusion criteria: Main renal arteries < 4 mm in diameter or < 20 mm treatable length, multiple renal arteries, renal artery stenosis > 50% or renal artery aneurysm in either renal artery, history of prior renal artery intervention including balloon angioplasty or stenting and unilateral (functional or morphological) kidney, > 1 inpatient hospitalisation for hypertensive crisis not related to nonadherence to medication within the previous year, type 1 diabetes mellitus and ≥ 1 episodes of orthostatic hypotension not related to medication changes, secondary hypertension
Interventions	Treatment group: N = 22, Renal denervation plus antihypertensive medications Control group: N = 19, Antihypertensive medications alone Renal denervation procedure: Ablation done with the Symplicity™ RDN system (Medtronic, Santa Rosa, CA, USA). Four to 6 ablation runs of 120 sec for each renal artery were delivered circumferentially to the renal artery wall from distal to proximal. Follow‐up: up to 6 months
Outcomes	Change in office BP Change in 24‐hour ABPM and home BP Incidence of major adverse events (composite of 1‐month all‐cause mortality, end‐stage renal disease, significant embolic event resulting in end‐organ damage, renal artery dissection or perforation requiring intervention, vascular complications, hospitalisation for hypertensive crisis or new renal artery stenosis > 70% confirmed on angiography within 6 months after randomisation)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not specified
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not specified
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts. Intention‐to‐treat analysis performed
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	High risk	Honoraria from Medtronic. Involvement of Medtronic in data collection and statistical analyses

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INSPIRED.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Belgium Setting: University
Participants	Number of patients randomised/analysed: 17/15 Age: ~48 years (range 33.6‐62.3) Males (%): 46 Office BP (mmHg): 166/101 24‐h ABPM (mmHg): 159/97 Daytime ABPM (mmHg): 164/102 Nght‐time ABPM (mmHg): 148/89 eGFR (mL/min/1.73 m²): 87 Creatinine (mg/dL): 0.9 Duration of hypertension (yrs): 10 Diabetes mellitus (%): 16 Smokers (%): 38 Antihypertensive drugs (n): 4.0 Antihypertensive treatment: ARBs (%): 100 CCBs (%): 94 β‐blockers (%): 72 Any diuretics (%): 89 Thiazide/thiazide like (%): 61 Loop diuretic (%): 14 Aldosteron antagonist (%): 69 Exclusion criteria: pregnancy, secondary hypertension, eGFR < 45 mL/min/1.73 m², unsuitable anatomy of renal arteries (diameter < 4 mm and length < 20 mm) including significant (≥ 50%) renal arterial stenosis, renal artery stent or single functional kidney, isolated systolic or isolated diastolic hypertension, body mass index ≥ 40 kg/m², unstable diabetes mellitus, major cardiovascular events within 6 months prior to enrolment, any serious medical condition, alcohol or substance abuse or psychiatric illnesses, patients on the waiting list of elective surgery
Interventions	Treatment group: n = 8 renal denervation plus usual medical treatment Control group: n = 9 usual medical treatment alone Renal denervation procedure: ablation done using the EnligHTN™ multi‐electrode denervation system performing four ablations simultaneously delivered at the mid/distal segment of the renal artery Follow‐up: up to 6 months
Outcomes	24‐hour SBP Change in eGFR Proportion of patients reaching and maintaining blood pressure control Acute and chronic procedural safety New renal artery stenosis of over 60% Decline in eGFR ≥ 25% Cardiovascular outcomes Quality of life was assessed by means of the EQ‐5D‐5L questionnaire, a standardised instrument to measure health status
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were randomized by means of a computerized random function with block size restriction".
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not specified
Incomplete outcome data (attrition bias) All outcomes	Low risk	2/17 (11.7%) dropouts in RDN group; per‐protocol analysis
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	Low risk	No evidence of other bias

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Moiseeva 2020‐B.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Romania Setting: Hospital
Participants	Number of patients randomised/analysed: 75/75 Comorbidity: None Diastolic dysfunction: 100% Antihypertensive treatment: Diuretics (%): 100 CCBs (%): 100 ARBs (%): 100
Interventions	Treatment group: Renal denervation plus daily treatment with losartan 100 mg, amlodipine 10 mg and indapamide 1.5 mg Control group (M): Daily treatment with losartan 100 mg, amlodipine 10 mg and indapamide 1.5 mg plus monoxidine 0.6 mg/day Control group (B): Daily treatment with losartan 100 mg, amlodipine 10 mg and indapamide 1.5 mg plus bisoprolol 10 mg/day Renal denervation procedure: Spyral Medtronic catheters Follow‐up: up to 6 months
Outcomes	Change in office BP values Change in 24‐hour ABPM Diastolic function parameters
Notes	Study in abstract version only
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not specified
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not specified
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not specified
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not specified
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	Unclear risk	Not specified

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Moiseeva 2020‐M.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Romania Setting: Hospital
Participants	Number of patients randomised/analysed: 75/75 Comorbidity: None Diastolic dysfunction: 100% Antihypertensive treatment: Diuretics (%): 100 CCBs (%): 100 ARBs (%): 100
Interventions	Treatment group: Renal denervation plus daily treatment with losartan 100 mg, amlodipine 10 mg and indapamide 1.5 mg Control group (M): Daily treatment with losartan 100 mg, amlodipine 10 mg and indapamide 1.5 mg plus monoxidine 0.6 mg/day Control group (B): Daily treatment with losartan 100 mg, amlodipine 10 mg and indapamide 1.5 mg plus bisoprolol 10 mg/day Renal denervation procedure: Spyral Medtronic catheters Follow‐up: up to 6 months
Outcomes	Change in office BP values Change in 24‐hour ABPM Diastolic function parameters
Notes	Study in abstract version only
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not specified
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not specified
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not specified
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not specified
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	Unclear risk	Not specified

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Oslo RDN 2014.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Norway Setting: University
Participants	Number of patients randomised/analysed: 19/19 Age: range 37 to 70 years, mean 60 Males (%): 89 Office BP (mmHg): 158/90 Diabetes mellitus (%): 26 Coronary artery disease (%): 35 Left ventricular hypertrophy (%): 58 Peripheral arteriosclerosis (%): 5 Previous stroke (%): 10 Hypercholesterolaemia (%): 31 Microalbuminuria (%): 37 Cystatin C (mg/L): 1.0 Antihypertensive drugs (n): 5.1 Antihypertensive treatment: Diuretics (%): 100 ACEIs/ARBs (%): 100 CCBs (%): ~80 Direct renin inhibitors (%): 10 β‐blockers (%): 73 α‐blockers (%): 37 Aldosterone antagonist (%): 47 Exclusion criteria: secondary and spurious hypertension, known primary hyperaldosteronism not adequately treated, eGFR < 45 mL/min/1.73 m², urine albumin/creatinine ratio > 50 mg/mmol, type 1 diabetes mellitus, stenotic valvular heart disease, myocardial infarction, unstable angina, or CVA in the prior 6 months, haemodynamically or anatomically significant renal artery abnormalities or stenosis > 50% or prior renal artery intervention, known primary pulmonary hypertension, known pheochromocytoma, Cushing's disease, coarctation of the aorta, hyperthyroidism or hyperparathyroidism
Interventions	Treatment group: N = 9, renal denervation plus baseline antihypertensive treatment Control group: N = 10, drug‐adjusted treatment Renal denervation procedure: renal denervation performed using a 6 French guide Symplicity catheter system. On average 8 (range 6 to 11) radiofrequency ablations were applied per renal artery. Follow‐up: up to 84 months
Outcomes	24‐hour ABPM Office BP Daytime ABPM Normalisation of haemodynamics: cardiac index, heart rate, stroke systemic vascular resistance index, pulse wave velocity (PWV), and central blood pressure Adverse events
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "randomisation performed using a permuted block randomisation list"
Allocation concealment (selection bias)	Low risk	Quote: "A hospital employee opened a sealed envelope arranged in a fixed order".
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes were reported.
Other bias	Unclear risk	Honoraria from Medtronic and Hemo Sapiens. Involvement of industry in data collection and analyses not specified

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Prague‐15.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Czech Republic Setting: University
Participants	Number of patients randomised/analysed: 101/101 Age: 58 years Males (%): 70 Office BP (mmHg): 157/91 24‐hour ABPM (mmHg): 148/85 Duration of hypertension (yrs): 17 Diabetes mellitus (%): 20 Coronary heart disease (%): 6 Smokers (%): 15 Statin users (%): 53 Creatinine (µmol/L): 86 Creatinine clearance (mL/s/1.73 m²): 1.6 Antihypertensive drugs (n): 5.3 Antihypertensive treatment: Diuretics (%): 100 ACEIs/ARBs (%): 100 CCBs (%): 89 β‐blockers (%): 67 α‐blockers (%): 50 Exclusion criteria: secondary hypertension, noncompliance with medical treatment, presence of any chronic renal disease (serum creatinine > 200 µmol/L), pregnancy, history of myocardial infarction or stroke in the previous 6 months, presence of severe valvular stenotic disease, anatomical abnormality or a variant structure of either renal artery, including aneurysm, stenosis, a reference diameter < 4 mm and a length < 20 mm, an increased bleeding risk (thrombocytopenia < 50.000 platelets/µL and an INR > 1.5)
Interventions	Treatment group: N = 51, renal denervation plus baseline medical therapy Control group: N = 50, intensified pharmacological treatment including spironolactone (PHAR) Renal denervation procedure: ablation involved ≥ 4 to 6 applications of low‐power (8 W) radiofrequency energy to each renal artery using the Symplicity renal denervation system Follow‐up: up to 24 months
Outcomes	24‐hour ABPM Office BP Average number of antihypertensive drugs used after 6 months Renal function (serum creatinine, creatinine clearance)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not specified
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label
Incomplete outcome data (attrition bias) All outcomes	Low risk	38/101 (37%) dropouts (7 in RD and 31 in PHAR group); intention‐to‐treat and per‐protocol analyses performed
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	Unclear risk	No apparent other sources of bias

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RELIEF 2012.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Czech Republic Setting: Hospital
Participants	Number of patients randomised/analysed: 23/23 Age: range 18 to 85 years Office BP (mmHg): ≥ 140 Exclusion criteria: secondary hypertension, eGFR < 45 mL/min/1.73 m², type 1 diabetes mellitus, renovascular abnormalities (renal artery stenosis, previous renal artery stenting or angioplasty), life expectancy < 1 year for any medical condition
Interventions	Treatment group: N = 11, bilateral RD with a saline‐irrigated catheter Control group: N = 12, sham procedure Renal denervation procedure: ablation performed with an off‐the‐shelf saline‐irrigated radiofrequency ablation catheter Sham procedure: angiography of the renal arteries (manipulation of catheter within the renal arteries without the delivery of any energy) Follow‐up: up to 3 months
Outcomes	24‐hour ABPM Office BP Serum creatinine
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not specified
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Single‐blind
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not specified
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not specified
Selective reporting (reporting bias)	High risk	Some prespecified outcomes were not reported.
Other bias	Unclear risk	No apparent other sources of bias

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ReSET 2015.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Denmark Setting: University and hospital
Participants	Number of patients randomised/analysed: 69/69 Age: range 30 to 70 years, mean: 56 Males (%): 74 Smokers (%): 17 Office BP (mmHg): 163/92 Daytime ABPM (mmHg): 159/94 Night‐time ABPM (mmHg): 138/80 ABPM (mmHg): 152/90 eGFR ≥ 60 (mL/min/1.73 m): 87% eGFR 45‐60 (mL/min/1.73 m): 7% eGFR 30‐45 (mL/min/1.73 m): 1.5% Duration of hypertension (years): 11.1 History of CVD (%): 10.5 LVMI (g/m²): 116 Type 2 diabetes (%): 28 Statin users (%): 42 Sleep apnea (CPAP treatment) (%): 10 Antihypertensive drugs (n): 4.1 Antihypertensive treatment: ACEIs (%): 49 ARBs (%): 61 Loop diuretic (%): 29 CCBs (%): 69 Direct renin inhibitors (%): 4 α‐blockers (%): 16 β‐blockers (%): 78 Aldosterone antagonists (%): 22 Centrally acting sympatholytic agents (%): 16 Exclusion criteria: pregnancy, no compliance, heart failure (NYHA 3 to 4), left ventricular ejection fraction < 50%. Unstable coronary heart disease, coronary intervention within 6 months, myocardial infarction within 6 months. Claudication. Orthostatic syncope within 6 months, secondary hypertension, permanent atrial fibrillation. significant heart valve disease. Clinically significant abnormal electrolytes, haemoglobin, liver enzymes and TSH. Second‐ and third‐degree heart block, macroscopic haematuria, proximal significant coronary stenosis, renal artery anatomy not suitable for renal artery ablation (stenosis, diameter < 4 mm, length < 20 mm, multiple renal arteries, severe calcifications)
Interventions	Treatment group: N = 36, renal denervation Control group: N = 33, sham procedure Renal denervation procedure: catheter‐based renal denervation by applying low power radiofrequency to the renal artery using the Ardian Medtronic Simplicity catheter. Four‐to‐six discrete, low‐power radio frequency treatments were applied to cover the entire circumference in a spiral manner along the length of each main renal artery. Follow‐up: up to 6 months
Outcomes	24‐hour, daytime and night‐time ABPM, after 1‐, 3‐ and 6‐month follow‐up Vasoactive hormones at baseline and after 1 month of follow‐up Coronary flow reserve (LAD), diastolic and systolic ventricular function. Left ventricular hypertrophy, LVM index Pulse wave velocity, augmentation index, central BP estimates Decline in eGFR ≥ 25% Safety records concerning BP, renal function, electrolyte disarrangement, stroke, TIA, myocardial infarction and symptomatic hypotension.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were randomised using a computer.
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not specified
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: “No patients were lost to follow‐up, and no patients were unblinded prematurely.”
Selective reporting (reporting bias)	High risk	Some prespecified outcomes were not reported.
Other bias	High risk	Quote: “A.K. has received speaker honoraria from Medtronic".

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SYMPATHY.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: The Netherlands Setting: Hospital
Participants	Number of patients randomised/analysed: 139/124 Mean Age: 61 Males (%): 35.8 Diabetes mellitus (%): 20 Cardiovascular disease history (%): 43 eGFR (mL/min/1.73 m²): 78.5 Office BP (mmHg): 169/96 Daytime systolic ABPM (mmHg): 160 ± 17 Daytime diastolic ABPM (mmHg): 93 ± 15 24‐h ABPM (mmHg): 157/90 Antihypertensive drugs (n): 3.5 Antihypertensive treatment: Diuretics (%): 65.8 Beta‐blocker (%): 61 ARBs (%): 30 CCBs (%): 62 Aldosterone antagonist (%): 5.5 Alpha‐blocker (%): 28 Centrally acting antihypertensive drug: 8 Other: 2 Exclusion Criteria: Pregnancy, type 1 diabetes mellitus, eGFR (mL/min/1.73 m²) < 20, chronic oxygen support or mechanical ventilation, primary pulmonary hypertension, white‐coat hypertension, previous renal denervation, secondary hypertension, significant renovascular abnormalities. Myocardial infarction, unstable angina pectoris or cerebrovascular accident < 180 days prior to enrolment. Blood clotting abnormalities, life expectancy < 12 months, renal arteries < 4 mm in diameter or < 20 mm in length or multiple renal arteries where the main renal arteries supply < 75% of the kidney. Pheochromocytoma, Cushing's disease, coarctation of the aorta
Interventions	Treatment group: N= 95, renal denervation plus usual medical treatment Control group: N= 44, usual medical treatment alone Renal denervation procedure: ablation done using the EnligHTN™ multi‐electrode denervation system performing four ablations simultaneously. One 60‐s ablation delivered at the mid/distal segment of the renal artery Follow‐up: up to 6 months
Outcomes	Daytime systolic ABPM 24‐hour ABPM Office systolic BP (SBP) 24‐hour urinary sodium excretion Change in the amount of antihypertensive medication Change in estimated Glomerular Filtration Rate (eGFR) Level of adherence Periprocedural complications Impact on quality of life
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote:"Randomization in a 2:1 ratio using a web‐based computerized approach, with stratification by hospital and estimated glomerular filtration rate"
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not specified
Incomplete outcome data (attrition bias) All outcomes	Low risk	8/139 (5.8%) dropout (5 in RDN and 3 in usual care group); modified intention‐to‐treat analysis
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	High risk	P.J. Blankestijn received grants from ZonMw, Dutch Kidney Foundation, Medtronic, and personal fees from Medtronic, during the conduct of the study.

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SYMPLICITY HTN‐2 2010.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Multicentre Setting: Hospital, university
Participants	Number of patients randomised/analysed: 106/100 Age: 58 years Males (%): 57 BP (mmHg): 178/98 Race (white) (%): 97 Diabetes mellitus (%): 97 Coronary artery disease (%): 13 Hypercholesterolaemia (%): 52 eGFR (mL/min/1.73 m²): 82 Serum creatinine (μmol/L): 85 Urine albumin‐to‐creatinine ratio (mg/g): 118 Cystatin C (mg/L): 0.9 Antihypertensive drugs (n): 5.3 Antihypertensive treatment: Diuretics (%): 90 ACEIs/ARBs (%): 95 CCBs (%): 81 Direct renin inhibitors (%): 17 β‐blockers (%): 76 α‐blockers (%): 26 Aldosterone antagonists (%): 17 Vasodilators (%): 16 Exclusion criteria: eGFR < 45 mL/min/1.73 m², type 1 diabetes mellitus, contraindications to MRI, substantial stenotic valvular heart disease, pregnancy or planned pregnancy during the study, history of myocardial infarction, unstable angina or cerebrovascular accident in the previous 6 months, haemodynamically significant renal artery stenosis, previous renal artery intervention or renal artery anatomy ineligible for treatment (< 4 mm diameter, < 20 mm length or more than one main renal arteries)
Interventions	Treatment group: N = 52, bilateral renal denervation plus baseline antihypertensive medications Control group: N = 54, baseline antihypertensive medications Renal denervation procedure: renal denervation with Symplicity catheter system. Four to six discrete, low‐power radio frequency treatments were applied along the length of both main renal arteries. Follow‐up: up to 6 months
Outcomes	Office BP Short‐ and long‐term safety profile: reduction of eGFR > 25% or new stenosis > 60%, composite cardiovascular end point (myocardial infarction, sudden cardiac death, new‐onset heart failure, death from progressive heart failure, stroke, aortic or lower limb revascularisation procedure, lower limb amputation, death from aortic or peripheral arterial disease, dialysis, death because of renal failure, hospital admission for hypertensive emergency unrelated to nonadherence or nonpersistence with drugs and hospital admission for atrial fibrillation)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not specified
Allocation concealment (selection bias)	Low risk	Quote: "Randomisation was done with sealed envelopes".
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Data analysers were not masked to treatment assignment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	6/100 (6%) dropouts (3 in RD and 3 in control group); quote: "all analyses were done with data for all patients at randomisation minus those lost to follow‐up".
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	High risk	Data were monitored, collected, and managed by the sponsor (Ardian).

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SYMPLICITY HTN‐3 2014.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: US Setting: Hospital, university
Participants	Number of patients randomised/analysed: 535/535 Age: 57 years Males (%): 62 Race: Black (%): 27 White (%): 70 Asian (%): 0.3 Other (%): 1.5 24‐hour ABPM (mmHg): 160/90 eGFR < 60 mL/min/1.73 m² (%): 9.5 Renal artery stenosis (%): 1.8 Obstructive sleep apnoea (%): 29 Stroke (%): 10 Transient ischaemic attack (%): 4 Peripheral artery disease (%): 4 Coronary artery disease (%): 26 Myocardial infarction (%): 8 Diabetes mellitus (%): 44 Hyperlipidaemia (%): 67 Smokers (%): 11 Hospitalisation for hypertensive crisis (%): 23 Hospitalisation for hypotension (%): 2 Antihypertensive drugs (n): 5.2 Antihypertensive treatment: Diuretics (%): 100 ACEIs (%): 45 ARBs (%): 52 CCBs (%): 72 Direct renin inhibitors (%): 7 β‐blockers (%): 86 α‐blockers (%): 12 Aldosterone antagonists (%): 25 Exclusion criteria: secondary causes of hypertension or more than one hospitalisation for hypertensive emergency in the previous year, primary pulmonary hypertension, 24‐h ABPM average SBP < 135 mmHg, eGFR < 45 mL/min/1.73 m², type 1 diabetes mellitus, chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnoea, renal artery stenosis > 50%, renal artery aneurysm, prior renal artery intervention, multiple renal arteries, renal artery diameter < 4 mm or treatable segment < 20 mm in length, myocardial infarction, unstable angina pectoris, syncope or a cerebrovascular accident within 6 months of the screening period, history of pheochromocytoma, Cushing’s disease, coarctation of the aorta, hyperthyroidism or hyperparathyroidism, pregnancy, nursing or planning to be pregnant
Interventions	Treatment group: N = 364, bilateral renal denervation plus baseline antihypertensive medications Control group: N = 171, sham procedure plus baseline antihypertensive medications Renal denervation procedure: Four to six ablations of up to 120 seconds delivered to the renal artery wall beginning at the distal end of the artery Sham procedure: angiography of the renal arteries Follow‐up: up to 6 months
Outcomes	24‐hour ABPM Office systolic BP Daytime and night‐time BP Incidence of major adverse events (composite of: all‐cause mortality, end‐stage renal disease, significant embolic event resulting in end‐organ damage, renal artery perforation or dissection requiring intervention, vascular complications, hospitalisation for hypertensive crisis not related to nonadherence with medications or new renal artery stenosis > 70%)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Randomization (2:1 ratio) is performed using an interactive voice response system".
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Single‐blind
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Outcome's assessors were blinded to the treatment. Blood pressure assessments were done by blinded, trained personnel".
Incomplete outcome data (attrition bias) All outcomes	Low risk	16/535 (3%) dropouts (14 in RD and 2 in sham procedure); ITT analysis performed
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	High risk	Quote: "Data were collected and analysed by the sponsor (Medtronic, Minneapolis, Minnesota) and independently validated by Harvard Clinical Research Institute (Boston, Massachusetts)".

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Warchol 2014.

*Study characteristics*
Methods	Study type: parallel‐group, RCT Country: Poland Setting: Institute of Cardiology
Participants	⦁ Number of patients randomised/analysed: 60/52 ⦁ Age: mean 55.3 ± 9.3 ⦁ Males (%): 80 ⦁ Hypertension duration: 15 ⦁ Smokers (%): 43 ⦁ Diabetes mellitus type 2 (%): 38 ⦁ Coronary heart disease (%): 30 ⦁ Office BP (mmHg): 161/95 ⦁ Office HR (bpm): 71 ⦁ 24‐h ABPM (mmHg): 149/88 ⦁ Mean daytime ABPM (mmHg): 151/90 ⦁ Mean night‐time ABPM (mmHg): 140/81 ⦁ Serum creatinine (μmol/L): 81 ⦁ eGFR (mL/min/1.73 m²): 92.5 ⦁ Cystatin C (mg/L): 0.9 ⦁ Obstructive sleep apnoea (apnea/hypopnoea index, AHI): 35 events/hour ⦁ Number of drugs used: 5.0 Exclusion criteria: renal artery abnormalities, eGFR < 60mL/min, previous TIA, stroke, heart failure, type 1 diabetes mellitus, implantable cardioverter defibrillator or pacemaker
Interventions	⦁ Treatment group: N = 30, RD plus antihypertensive medications ⦁ Control group: N = 30, antihypertensive medications alone ⦁ Renal denervation procedure: ablation done using a catheter‐based procedure (Symplicity). Discrete radio‐frequency ablations of ≤ 8 W were applied, lasting ≤ 2 minutes each, to obtain ≤ 6 ablations separated both longitudinally and rotationally within each renal artery. ⦁ Follow‐up: up to 6 months
Outcomes	⦁ Office BP ⦁ 24‐hour, daytime and night‐time ABPM ⦁ Change in OSA severity ⦁ Fasting plasma glucose and insulin concentration ⦁ Echocardiographic measures ⦁ Estimated GFR ⦁ Cardiovascular events and arrhythmias
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not specified
Allocation concealment (selection bias)	Unclear risk	Not specified
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label
Incomplete outcome data (attrition bias) All outcomes	Low risk	8/60 (13.3%) dropouts (2 in RD and 6 in control group). Analysis performed not specified
Selective reporting (reporting bias)	Low risk	All the prespecified outcomes have been reported.
Other bias	Low risk	Quote: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript".

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^{ABPM: ambulatory blood pressure monitoring} ^{ACEI: angiotensin–converting enzyme inhibitors} ^{AHI: apnea hypopnea index} ^{ARB: angiotensin receptor blockers} ^{bpm: beats per minute} ^{BP: blood pressure} ^{BPV: blood pressure variability} ^{CCB: calcium channel blocker} ^{CPAP: continuous positive airway pressure therapy} ^{CVA: cerebrovascular accident} ^{CVD: cardiovascular disease} ^{DM: diabetes mellitus} ^{eGFR: estimated glomerular filtration rate} ^{EQ‐5D‐5L: euroQol five‐dimensional five‐levels} ^{HR: hearth rate} ^{INR: international normalized ratio} ^{ITT: intention to treat} ^{LAD: left anterior descending artery} ^{LV: left ventricle} ^{LVM: left ventricular mass} ^{LVMI: left ventricular mass index} ^{MRI: magnetic resonance imaing} ^{NYHA: New York Heart Association} ^{OSA: obstructive sleep apnea} ^{PHAR: pharmacological treatment} ^{PRD: percutaneous renal denervation} ^{PWV: pulse wave velocity} ^{RAS: renin‐angiotensin system} ^{RCT: randomized clinical trial} ^{RD: renal denervation} ^{RDN: renal denervation} ^{SBP: systolic blood pressure} ^{SSAHT: standardised stepped‐care antihypertensive treatment} ^{TIA: transient ischaemic attack} ^{TSH: thyroid stimulating hormone} ^{UAE: urinary albumine excretion} ^{W: wave}

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Ahmed 2012b	Not RCT
Ahmed 2013	Wrong population
Azizi 2018	Wrong population
Azizi 2019	Wrong population
Azizi M 2019	Wrong population
Baev 2017	Wrong intervention
Bohm 2018	Wrong population
Bohm 2019	Wrong population
Bohm 2020	Wrong population
Bohm 2020b	Wrong population
Bohm 2020c	Wrong population
Bosch 2020	Not RCT
Brandt 2012	Not RCT
Brandt 2012a	Not RCT
Chen 2017	Not RCT
Chen 2019	Wrong population
Chen 2019b	Wrong population
ChiCTR‐ONC‐12002901	Not RCT
ChiCTR‐ONC‐13003231	Wrong intervention
ChiCTR‐TNC‐12002900	Not RCT
Courand 2016	Wrong outcome
Courand 2017	Wrong outcome
de Jager, R. 2018	Wrong outcome
De Jager 2017	Wrong outcome
Dimitriadis 2017	Wrong population
DRKS00005865	Wrong intervention
DRKS00006405	Wrong population
DRKS00006420	Not RCT
DRKS00006493	Wrong population
Eikelis 2017	Not RCT
EnligHTN III	Not RCT
Esler 2013	Wrong population
Ewen 2014	Not RCT
Fadl Elmula 2013	Not RCT
Fengler 2018	Not RCT
Forssell 2020	Wrong intervention
Grassi 2015	Not RCT
Hamdidouche 2019	Wrong intervention
Hering 2013	Not RCT
Kampmann 2016	Not RCT
Kandzari 2016	Wrong population
Kandzari 2018	Wrong population
Karbasi‐Afshar 2013	Not RCT
Kario 2018	Wrong population
Kario 2019	Wrong intervention
Kario 2020	Wrong population
Kario K 2018	Wrong population
Katholi 2014	Wrong population
Kjeldsen 2014	Not RCT
Krum 2014	Not RCT
Li 2019	Wrong population
Li 2019	Wrong intervention
Lobo 2015	Not RCT
Lurz 2020	Not RCT
Mahfoud 2011	Wrong population
Mahfoud 2011a	Wrong population
Mahfoud 2012	Not RCT
Mahfoud 2013	Not RCT
Mahfoud 2014	Not RCT
Mahfoud 2019	Wrong population
Mahfoud 2020	Not RCT
Mahfoud 2020b	Not RCT
Mahfoud 2020c	Wrong population
NCT01117025	Wrong intervention
NCT01465724	Not RCT
NCT01583881	Wrong population
NCT01631370	Not RCT
NCT01635998	Wrong population
NCT01687725	Not RCT
NCT01733901	Wrong population
NCT01814111	Wrong population
NCT01848314	Not RCT
NCT01873352	Wrong population
NCT01888315	Not RCT
NCT01897545	Wrong intervention
NCT01901549	Wrong population
NCT01907828	Wrong population
NCT01932450	Wrong population
NCT02016573	Wrong population
NCT02057224	Not RCT
NCT02115100	Wrong population
NCT02115230	Wrong population
NCT02155790	Not RCT
NCT02164435	Not RCT
NCT02272920	Wrong population
NCT02559882	Wrong intervention
NCT02667912	Wrong intervention
NCT03261375	Wrong population
NCT03465917	Not RCT
NCT03511313	Wrong population
NCT04248530	Wrong population
NCT04264403	Wrong population
NCT04307836	Wrong population
NCT04311086	Not RCT
NCT04535050	Wrong population
Palionis 2016	Not RCT
Pekarskiy 2016	Wrong intervention
Pekarskiy 2020	Wrong intervention
Persu 2018	Not RCT
Petrov 2019	Wrong intervention
Pokushalov 2012	Wrong intervention
Pokushalov 2012a	Wrong intervention
Pokushalov 2012b	Wrong intervention
Pokushalov 2014	Wrong intervention
Pokushalov 2014a	Not RCT
Pokushalov 2014b	Wrong intervention
RADIANCE‐HTN SOLO	Wrong population
RADIANCE II	Wrong population
RAPID	Not RCT
ReD	Not RCT
REDUCE HTN:REINFORCE	Wrong population
Ripp 2019	Not RCT
RNS‐NTR 4384	Not RCT
RSDAH	Wrong population
Sanders 2016	Wrong population
Saxena 2017	Wrong intervention
Saxena 2018	Wrong intervention
Scalise 2020	Not RCT
Schmieder 2017	Wrong intervention
Schmieder 2018	Wrong intervention
Shipman 2014	Not RCT
Shugushev 2019	Wrong intervention
Shugushev 2019b	Wrong intervention
Sievert 2014	Not RCT
Sitkova 2020	Wrong intervention
SPYRAL HTN‐OFF MED	Wrong population
SPYRAL HTN‐ON MED	Wrong population
Stoiber 2018	Not RCT
SYMPLICITY 2011	Not RCT
SYMPLICITY AF	Wrong population
TARGET BP OFF‐MED	Wrong population
Townsend 2017	Wrong population
Tsioufis 2016	Wrong population
UMIN000012020	Not RCT
Wage 2015	Wrong outcome
Waksman 2016	Wrong outcome
WAVE IV	Wrong intervention
Wave VI	Wrong intervention
Weber 2018	Wrong population
Weber 2020	Wrong population
Witkowski 2011	Not RCT
Xiang 2014	Wrong intervention
Yin 2013	Wrong population
Zhang 2014	Not RCT

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RCT: randomized clinical trial

Characteristics of ongoing studies [ordered by study ID]

ALLEGRO‐HTN.

Study name	Renal denervation by Allegro System in patients with resistant hypertension
Methods	Study type: parallel‐group, RCT Country: China Setting: Hospital
Participants	Estimated number of patients: 160 Age: range 18 to 65 years Office BP (mmHg): ≥ 160/100 (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) ABPM (mmHg): ≥ 140/90 eGFR (mL/min/1.73 m²): ≥ 45 Exclusion criteria: pregnancy, type 1 diabetes mellitus, secondary hypertension. ICD or pacemaker, myocardial infarction, unstable angina, syncope, cerebrovascular accident in the previous 6 months. Intravascular thrombosis or unstable atherosclerotic plaques, significant valvular heart disease. Renal artery stenosis (≥ 50%) or renal artery aneurysm in either renal artery, history of prior renal artery intervention including balloon angioplasty or stenting. Multiple renal arteries where the main renal artery is estimated to supply < 75% of the kidney. Main renal arteries with < 4 mm diameter or with < 20 mm treatable length (by visual estimation), renal artery abnormalities
Interventions	Treatment group: renal angiography followed by renal sympathetic denervation Control group: renal angiography alone Renal denervation procedure: Allegro Renal Denervation System (AngioCare) Follow‐up: up to 48 months
Outcomes	Change in office SBP from baseline to 6 months Change in average 24‐hour SBP by ABPM from baseline to 6 months Incidence of major adverse events (MAE) at 1 month post‐randomisation Office SBP and DBP at 1, 3, 6 months post‐randomisation Patient‐recorded home systolic blood pressure at 1, 3, 6 months post‐randomisation MAE at 6‐month post‐randomisation, including new renal artery stenosis > 60%
Starting date	May 2013
Contact information	Xiongjing Jiang: jxj103@hotmail.com
Notes

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DEPART.

Study name	Study of catheter‐based renal denervation therapy in hypertension (DEPART)
Methods	Study type: parallel‐group, RCT Country: Belgium Setting: Hospital
Participants	Estimated number of patients: 240 Age: range 18 to 85 years Office BP (mmHg): ≥ 135/85 eGFR (mL/min/1.73 m²): ≥ 30 Exclusion criteria: unsuitable anatomy of renal arteries (diameter < 4 mm and length < 20 mm) including significant (≥ 50%) renal arterial stenosis, renal artery stent or single functional kidney. Secondary hypertension, previous nephrectomy, contrast agent allergy, hyperthyroidia
Interventions	Treatment group: renal angiography followed by renal sympathetic denervation Control group: renal angiography alone Renal denervation procedure: radiofrequency catheter‐based therapy for renal denervation. Four‐to‐six low‐power radio frequency treatments along the length of both main renal arteries Follow‐up: up to 48 months
Outcomes	24‐hour SBP Change in eGFR and 24‐h urine sample measure Baroreflex sensitivity Biological markers of acute kidney injury
Starting date	January 2012
Contact information	Contact: ARGACHA Jean Francois, MD Jean.Francois.Argacha@erasme.ulb.ac.be
Notes

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EnligHTN IV.

Study name	Multi‐center, randomized, single‐blind, sham controlled clinical investigation of renal denervation for uncontrolled hypertension (EnligHTN IV)
Methods	Study type: parallel‐group, RCT Country: US Setting: University and hospital
Participants	Estimated number of patients: 590 Age: range 18 to 80 years Office BP (mmHg): ≥ 160 Systolic ABPM ≥ 140 mmHg (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) eGFR (mL/min/1.73 m²): ≥ 45 Exclusion criteria: pregnancy, type 1 diabetes mellitus, chronic oxygen support or mechanical ventilation, primary pulmonary hypertension. Previous renal denervation, secondary hypertension, significant renovascular abnormalities. Myocardial infarction, unstable angina pectoris, or cerebrovascular accident < 180 days prior to enrolment. Blood clotting abnormalities, life expectancy < 12 months. Renal arteries < 4 mm in diameter or < 20 mm in length or multiple renal arteries where the main renal arteries supply < 75% of the kidney, abdominal aortic aneurysm (AAA), pheochromocytoma, Cushing's disease, coarctation of the aorta, hyperthyroidism and hyperparathyroidism
Interventions	Treatment group: renal denervation Control group: sham procedure Renal denervation procedure: renal artery ablation with the EnligHTN™ Renal Denervation System Follow‐up: up to 36 months
Outcomes	Proportion of subjects who experience any major adverse event (MAE) Reduction of office systolic BP at 6 months Procedure‐related adverse events Incidence of achieving ≥ 10 mmHg, ≥ 15 mmHg, and ≥ 20 mmHg reductions in office BP Reduction in ABPM
Starting date	October 2013
Contact information	NA
Notes

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ENSURE.

Study name	Effect of renal denervation on arterial stiffness and haemodynamics in patients with uncontrolled hypertension (ENSURE)
Methods	Study type: parallel‐group, RCT Country: China Setting: Hospital
Participants	Estimated number of patients: 400 Age: range 18 to 80 years Office BP (mmHg): ≥ 160/100 (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) ABPM (mmHg): ≥ 140/90 eGFR (mL/min/1.73 m²): ≥ 45 Exclusion criteria: pregnancy, type 1 diabetes mellitus, chronic oxygen support or mechanical ventilation, primary pulmonary hypertension, ABPM 24‐hour average SBP < 135 mmHg
Interventions	Treatment group: Renal denervation Control group: Baseline antihypertensive medications Renal denervation procedure: MDT‐2211 Renal Denervation System Follow‐up: up to 36 months
Outcomes	Change in 24‐hour ambulatory aortic and brachial blood pressure and blood pressure variability Incidence of major adverse events through 1‐month post‐randomisation Change in asymptomatic organ damage (including electrocardiographically or echocardiographically diagnosed left ventricular hypertrophy, carotid intima‐media thickness or plaque, microalbuminuria, pulse wave velocity)
Starting date	September 2014
Contact information	Yawei Xu; yizshcn@gmail.com
Notes

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KPS.

Study name	Renal protection using sympathetic denervation in patients with chronic kidney disease (KPS)
Methods	Study type: parallel‐group, RCT Country: Czech Republic Setting: University/hospital
Participants	Estimated number of patients: 40 Age: range 18 to 80 years Office SBP (mmHg): ≥ 140 mmHg (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) eGFR (mL/min/1.73 m²): ≤ 45 Exclusion criteria: pregnancy, type 1 diabetes mellitus, significant valvular disease, renovascular abnormalities, secondary hypertension, white coat hypertension
Interventions	Treatment group: renal denervation and optimal medical therapy Control group: optimal medical therapy alone Follow‐up: up to 60 months
Outcomes	Changes of eGFR Changes in proteinuria (microalbuminuria) Changes in Cystatin C values Time to the development of end‐stage renal disease (ESRD)/haemodialysis Combined renal end point All‐cause mortality Cardiovascular mortality Changes of systolic and diastolic blood pressure at 6 months Changes in concentration of blood urea nitrogen (BUN), creatinine in 6 months Changes in cardiac structure and function Changes in renal resistive index
Starting date	November 2013
Contact information	Jean Claude Lubanda, Ass.Prof. MD; Jean‐Claude.Lubanda@vfn.cz
Notes

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NCT01848275.

Study name	Full length versus proximal renal arteries ablation
Methods	Study type: parallel‐group, RCT Country: China Setting: University
Participants	Estimated number of patients: 40 Age: > 18 Office SBP (mmHg): ≥ 160 eGFR (mL/min/1.73 m²): ≥ 45 Exclusion criteria: pregnancy, type 1 diabetes mellitus, significant valvular disease, ICD, renovascular abnormalities, secondary hypertension, white coat hypertension
Interventions	Treatment group: full length renal denervation by the Thermocool®R catheter Control group: proximity renal denervation by the Thermocool®R catheter Follow‐up: up to 36 months
Outcomes	Office BP ABPM Ablation‐related complications
Starting date	March 2011
Contact information	Yuehui Yin, MD; yinyh63@163.com
Notes

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NCT01918111.

Study name	Effects of renal denervation for resistant hypertension on exercise diastolic function and regression of atherosclerosis and the evaluation of new methods predicting a successful renal sympathetic denervation (RENEWAL‐EXERCISE, ‐REGRESS, and ‐PREDICT trial From RENEWAL RDN Registry)
Methods	Study type: cross‐over, RCT Country: Republic of Korea Setting: University
Participants	Estimated number of patients: 52 Age: range 20 to 85 years BP ≥ 140/90 mmHg or ≥ 130/80 mmHg for patients with diabetes (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) Exclusion criteria: Haemodynamically or anatomically significant renal artery abnormalities, main renal arteries < 4 mm in diameter or < 20 mm in length or prior renal artery intervention, eGFR < 30 mL/min/1.73m², using the MDRD formula. Valvular heart disease, history of congestive heart failure with left ventricular ejection fraction < 35%, ST‐segment elevation MI within 48 hours, scheduled or planned surgery or cardiovascular intervention in the 6 months after procedure. Chronic diseases with life expectancy < 1 year, hormone replacement treatment and/or oral contraceptives, pregnant, nursing or planning to be pregnant, chronic liver cirrhosis
Interventions	Treatment group: renal denervation Control group: adenosine infusion treatment Renal denervation procedure: catheter‐based renal denervation performed via common femoral artery with standard endovascular technique and Simplicity catheter Follow‐up: up to 24 months
Outcomes	Change in BP at 6 and 12 months post‐procedure
Starting date	September 2013
Contact information	Yangsoo Jang, MD 82‐2‐2228‐8460, jangys1212@yuhs.ac
Notes

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NCT01968785.

Study name	Renal denervation in patients with uncontrolled blood pressure
Methods	Study type: parallel‐group, RCT Country: US Setting: University
Participants	Estimated number of patients: 20 Age: range 18 to 85 years Office SBP (mmHg): ≥ 160 (≥ 150 mmHg for type 2 diabetics) (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) eGFR (mL/min/1.73 m²): ≥ 45 Exclusion criteria: pregnancy, type 1 diabetes mellitus, chronic oxygen support or mechanical ventilation, primary pulmonary hypertension, previous renal denervation. Secondary hypertension, significant renovascular abnormalities, myocardial infarction, unstable angina pectoris, or cerebrovascular accident < 180 days prior to enrolment. Blood clotting abnormalities, life expectancy < 12 months, renal arteries < 4 mm in diameter or < 20 mm in length or multiple renal arteries where the main renal arteries supply < 75% of the kidney, abdominal aortic aneurysm (AAA). Pheochromocytoma, Cushing's disease, coarctation of the aorta, hyperthyroidism, hyperparathyroidism
Interventions	Treatment group: beta radiation dosage of 50 Gy during renal denervation procedure Control group: beta radiation dosage of 25 Gy during renal denervation procedure Follow‐up: up to 24 months
Outcomes	Safety (need for intervention to treat renal artery injury induced by the procedure within 6 months) Decrease in SBP and DBP ≥ 10 mmHg at six months following the procedure Effects on blood pressure Acute procedural safety; renal artery dissection or perforation requiring intervention and serious groin complications specifically eGFR drop > 25% or new renal artery stenosis > 60% confirmed by angiogram at six months following renal artery brachytherapy procedure Medication changes Serious adverse events
Starting date	August 2013
Contact information	Ron Waksman, MD
Notes

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NCT02021019.

Study name	Renal denervation to improve outcomes in patients with end‐stage renal disease
Methods	Study type: parallel‐group, RCT Country: Australia Setting: University
Participants	Estimated number of patients: 100 Age: range 18 to 85 years Office SBP (mmHg): ≥ 140/90 End‐stage renal disease Exclusion criteria: myocardial infarction, unstable angina, cerebrovascular accident within 3 months of the screening visit
Interventions	Treatment group: renal denervation Control group: usual care Renal denervation procedure: ablation done using catheter‐based (Symplicity) radiofrequency approach Follow‐up: up to 24 months
Outcomes	Office SBP change 6 months after the procedure
Starting date	January 2014
Contact information	Markus P Schlaich, MD Baker IDI Heart and Diabetes Institute
Notes

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NCT02346045.

Study name	Effect of renal denervation in end staged renal disease with resistant hypertension
Methods	Study type: parallel‐group, RCT Country: South Korea Setting: Hospital
Participants	Estimated number of patients: 40 Age: range 18 to 90 years Office BP (mmHg): ≥ 160 (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) Haemodialysis patients Exclusion criteria: pregnancy, type 1 diabetes mellitus, secondary hypertension. ICD or pacemaker, myocardial infarction, unstable angina pectoris, syncope, cerebrovascular accident in the previous 6 months. Intravascular thrombosis or unstable atherosclerotic plaques, significant valvular heart disease, renal artery stenosis (≥ 50%) or renal artery aneurysm in either renal artery, history of prior renal artery intervention including balloon angioplasty or stenting, multiple renal arteries where the main renal artery is estimated to supply < 75% of the kidney. Main renal arteries with < 4 mm diameter or with < 20 mm treatable length (by visual estimation). Renal artery abnormalities
Interventions	Treatment group: renal sympathetic denervation + medical therapy Control group: sham procedure + medical therapy Renal denervation procedure: renal denervation from distal to proximal portion by a Symplicity radiofrequency ablation catheter. Four to five ablations per each renal artery Follow‐up: up to 24 months
Outcomes	Change in office SBP Change in office DBP Change in ABPM Change in plasma norepinephrine Change in pulse wave velocity
Starting date	September 2014
Contact information	Kiyuk Chang, MD, PhD; kiyuk@40catholic.ac.kr
Notes

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NCT02444442.

Study name	The Australian SHAM controlled clinical trial of renal denervation in patients with resistant hypertension
Methods	Study type: parallel‐group, RCT Country: Australia Setting: Hospital
Participants	Estimated number of patients: 105 Age: range 18 to 85 years Systolic BP ≥ 140 mmHg and ambulatory daytime average ≥ 130 mmHg despite concurrent treatment with ≥ 3 antihypertensive drugs Exclusion criteria: renal artery anatomy ineligible for treatment, eGFR < 15 mL/min/1.73m² (using MDRD calculation), myocardial infarction, unstable angina or cerebrovascular accident within 3 months of screening visit, life expectancy < 12 months, pregnancy
Interventions	Treatment group: renal denervation Control group: sham procedure Renal denervation procedure: radiofrequency catheter‐based therapy for renal denervation Follow‐up: up to 36 months
Outcomes	Change in ambulatory SBP from baseline to 6 months Change in mean 24‐hour SBP from baseline to 6 months Change in mean office SBP from baseline to 6 months Change in left ventricular function 6 months post‐procedure Change in serum biochemistry (plasma renin activity, aldosterone levels, estimated Glomerular Filtration Rate (eGFR), inflammatory markers, fasting glucose, fasting insulin, C‐peptide, Homeostasis Model Assessment (HOMA) index, lipid profile) 6 months post‐procedure Change in urine biochemistry (urinary albumin creatinine ratio (UACR), 24‐hour urinary creatinine clearance, sodium) 6 months post‐procedure Change in quality of life
Starting date	June 2015
Contact information	Markus P Schlaich, Professor +61 3 85321502, Markus.Schlaich@bakeridi.edu.au Murray Esler, Professor +61 3 85321338, Murray.Esler@bakeridi.edu.au
Notes

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NCT02608632.

Study name	High frequency guided renal artery denervation for improving outcome of renal ablation procedure
Methods	Study type: parallel‐group, RCT Country: Russia Setting: Research Institute/hospital
Participants	Estimated number of patients: 170 Age: range 18 to 80 years Office BP (mmHg): ≥ 140/90 mm Hg and < 160/100 mm Hg (moderate resistant hypertension) or ≥160/100 mm Hg (severe resistant hypertension), despite treatment with 3 antihypertensive drugs (including a diuretic) eGFR (mL/min/1.73 m²): ≥ 45 (MDRD formula) Exclusion criteria: secondary hypertension, severe renal artery stenosis or dual renal arteries, congestive heart failure, left ventricular ejection fraction < 35%, previous renal artery stenting or angioplasty, type 1 diabetes mellitus
Interventions	Treatment group: renal denervation guided by HFS Control group: renal denervation as standard procedure Renal denervation guided by HFS: high‐frequency stimulation (HFS) used before the initial and after each radiofrequency (RF) delivery within the renal artery. Ablations of 8 to 12 watts applied from the first distal main renal artery bifurcation all the way back to the ostium and performed both longitudinally and rotationally within each renal artery Renal denervation as standard procedure: ablations of 8 to 12 watts applied from the first distal main renal artery bifurcation all the way back to the ostium and performed both longitudinally and rotationally within each renal artery Follow‐up: 12 months
Outcomes	Number of responders to RD procedure up to 12 months Incidence of adverse events through 12 months after procedure
Starting date	February 2013
Contact information	NA
Notes

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NCT02900729.

Study name	Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial
Methods	Study type: parallel‐group, RCT Country: China Setting: University and hospital
Participants	Estimated number of patients: 254 Age: range 18 to 80 years 24 hours ambulatory SBP ≥ 135 mm Hg and office SBP ≥ 140 mmHg/office diastolic blood pressure (DBP) ≥ 90 mm Hg after 4 weeks’ standardised triple therapy Exclusion criteria: Acute or serious systemic infection. Renal artery interventional therapy. Lacks suitable renal artery anatomy. Myocardial infarction, unstable angina pectoris, syncope, or a cerebrovascular accident within 3 months of the screening period, or atherosclerosis, intravascular thrombosis. Aortic dissection aneurysm. Primary pulmonary hypertension. eGFR less than 40 mL/min/1.73 m². Coronary heart disease requiring beta‐blockers. Class III‐IV heart failure or left ventricular ejection fraction < 45%. Atrial fibrillation. Significant bleeding tendency or blood system disease(s). Malignancy or end‐stage disease(s). Secondary hypertension. Type 1 diabetes mellitus
Interventions	Treatment group: RDN using a 5F saline micro‐irrigated RFA plus antihypertensive medication Control group: treatment with antihypertensive medication alone Follow‐up: up to 6 months
Outcomes	Change in 24 hours average ambulatory SBP Change in office systolic/diastolic BP from baseline to 6 months post‐randomisation Incidence of achieving target BP at 6 months post‐randomisation. Target BP was defined as daytime ambulatory BP < 135/85 mm Hg, night‐time ambulatory BP < 120/70 mm Hg, or average 24 hours ambulatory BP < 130/80 mm Hg. Incidence of substantially adjusting antihypertensive medications at 6 months post‐randomisation. A substantial adjustment of antihypertensive medications was defined as any change in the number or type of antihypertensive medications, or a ≥ 50% dose change in the last 2 weeks with respect to any ongoing antihypertensive medications. Incidence of achieving reductions of ≥ 5 mm Hg, ≥ 10 mm Hg, ≥ 15 mm Hg and ≥ 20 mm Hg in BP, including ambulatory, office and home BP at 6 months post‐randomisation The safety endpoints mainly included any adverse events, change in renal function, other laboratory test, and cardiovascular complication.
Starting date	October 2016
Contact information	Dr Junbo Ge; jbge@zs‐hospital.sh.cn
Notes

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NTR3444.

Study name	Comparison of renal sympathetic denervation with spironolactone in patients with still a high blood pressure despite the use of 3 different antihypertensive agents
Methods	Study type: parallel‐group, RCT Country: The Netherlands Setting: Hospital
Participants	Estimated number of patients: not provided Age: range 18 to 75 years Treatment‐resistant hypertension Exclusion criteria: secondary hypertension, renal arteries inaccessible for endovascular denervation, suboptimal dosing of BP‐lowering medication, noncompliant to treatment, white coat hypertension, pregnancy, eGFR < 45 mL/min/1.73 m², use of vitamin K antagonist that can not be discontinued for a short period, spironolactone intolerance, myocardial infarction or cerebrovascular accident 3 months prior to randomisation, life expectancy < 2 years
Interventions	Treatment group: renal denervation Control group: antihypertensive treatment + spironolactone Renal denervation procedure: catheter‐based renal denervation Follow‐up: up to 6 months
Outcomes	Between‐group difference in 24‐hour ambulatory BP after 6 months of follow‐up Between‐group difference in quality of life score
Starting date	June 2012
Contact information	A Van den Meiracker, MD, PhD +31‐10‐4639222, a.vandenmeiracker@erasmusmc.nl
Notes

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PaCE.

Study name	A study of renal denervation in patients with treatment resistant hypertension (PaCE)
Methods	Study type: parallel‐group, RCT Country: Canada Setting: Hospital
Participants	Estimated number of patients: 100 Age: range 18 to 85 years eGFR (mL/min/1.73m²): ≥ 45 Office SBP ≥ 160 mmHg (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) Baseline average systolic ABPM ≥ 135 mmHg Exclusion criteria: pregnancy, type 1 diabetes mellitus, chronic oxygen support or mechanical ventilation, primary pulmonary hypertension, previous renal denervation, secondary hypertension, significant renovascular abnormalities. Myocardial infarction, unstable angina pectoris or cerebrovascular accident < 180 days prior to enrolment. Blood clotting abnormalities, life expectancy < 12 months, renal arteries < 4 mm in diameter or < 20 mm in length or multiple renal arteries where the main renal arteries supply < 75% of the kidney. Pheochromocytoma, Cushing's disease, coarctation of the aorta
Interventions	Treatment group: early renal denervation Control group: delayed renal denervation (6 months after patient's randomisation) Renal denervation procedure: catheter‐based renal denervation by applying low power radiofrequency to the renal artery using the Ardian Medtronic Simplicity catheter Follow‐up: up to 24 months
Outcomes	Average systolic ABPM Proportion of patients achieving target SBP Average daytime and night‐time systolic ambulatory BP Variability of 24‐hour ambulatory systolic BP Average office BP using an approved, automated office BP device Hypertensive medication complexity index (MRCI) Number of hypertensive medications Periprocedural mean cost per patient in Canadian dollars Generic quality of life (EQ‐5D) Body mass index (BMI) 24‐hour urine sodium Acute periprocedural renal injury Creatinine clearance measured on 24‐hour urine Vascular complications Evidence of renal artery stenosis compared to pre‐procedure (determined by renal imaging, CT or MRA) for early intervention group Composite cardiovascular end points Microalbumin to creatinine ratio (MACR) from random urine sample
Starting date	October 2013
Contact information	Harindra C. Wijeysundera, MD
Notes

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RADIANCE‐HTN.

Study name	A study of the ReCor Medical Paradise System in clinical hypertension (RADIANCE‐HTN), Trio cohort
Methods	Study type: parallel‐group, RCT Country: Germany Setting: Hospital and university
Participants	Estimated number of patients: 292 Age: range 18 to 75 years TRIO Cohort: Average seated office BP ≥ 140/90 mmHg Daytime ABP ≥ 135/85 mmHg and < 170/105 mmHg after 4‐week stabilisation period Average seated office BP ≥ 140/90 mmHg at screening visit while on a stable regimen of at least 3 antihypertensive medications of different classes including a diuretic for at least 4 weeks prior to consent Exclusion criteria: Renal artery anatomy on either side, ineligible for treatment. Single functioning kidney. Abnormal kidney tumours. Renal artery with aneurysm. Renal stent or history of renal artery angioplasty. Aortic stent or history of aortic aneurysm. Prior renal denervation procedure. Fibromuscular disease of the renal arteries. Presence of renal artery stenosis of any origin ≥ 30%. Secondary hypertension not including sleep apnoea. Type I diabetes mellitus or uncontrolled type II diabetes. History of chronic active inflammatory bowel disorders such as Crohn's disease or ulcerative colitis. eGFR < 40 mL/min/1.73 m². Any history of cerebrovascular event within 3 months prior to consent. Any history of severe cardiovascular event within 3 months prior to consent. Atrial tachyarrhythmia. Active implantable medical device. Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnoea. Primary pulmonary hypertension. Pregnant, nursing or planning to become pregnant
Interventions	Treatment group: Renal denervation Control group: Pharmacological treatment; Single pill, triple fixed dose (valsartan 160 mg/amlodipine 10 mg/HCTZ 25 mg or olmesartan 40 mg/amlodipine 10 mg/HCTZ 25 mg) Renal denervation procedure: Ablation done with Paradise System. Ultrasound energy delivered circumferentially for 7 seconds to thermally disrupt the renal sympathetic nerves at depths of 1‐6 mm Follow‐up: up to 36 months
Outcomes	Primary outcome: Mean reduction in average daytime ambulatory systolic BP Secondary outcome: Reduction in average 24‐hr/night‐time ambulatory systolic BP Reduction in average daytime/24‐hr/night‐time diastolic BP All‐cause mortality Hypertensive or hypotensive emergency resulting in hospitalisation Hospitalisation for heart failure Stroke, transient ischaemic attack, cerebrovascular accident Acute myocardial infarction End‐stage renal disease Renal artery or vascular complications requiring intervention Significant embolic events resulting in end‐organ damage Procedure‐related pain lasting > 2 days Acute renal injury Significant (> 50%) and severe (> 75%) new‐onset renal stenosis as diagnosed by duplex ultrasound and confirmed by renal CTA/MRA or as diagnosed/confirmed by study‐defined renal CTA/MRA at 12 months Major access site complications
Starting date	March 2016
Contact information	Michel Azizi, MD, PhD Ajay J Kirtane, M.D
Notes	Prior to randomisation, subjects will be hypertensive in the absence of hypertension medication (SOLO) or despite the presence of a stabilised, single pill, triple, fixed‐dose antihypertensive medication regimen (TRIO).

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RAPID II.

Study name	Rapid renal sympathetic denervation for resistant hypertension II (RAPID II)
Methods	Study type: parallel‐group, RCT Country: Italy Setting: Hospital/university
Participants	Estimated number of patients: not provided Age: range 18 to 75 years SBP (mmHg): ≥ 160 (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) Exclusion criteria: pregnancy, type 1 diabetes mellitus, renal anatomy unsuitable for treatment, significant valvular heart disease, scheduled or planned surgery within 6 months of study entry
Interventions	Treatment group: bilateral renal ablation plus antihypertensive medications Control group: optimal medical therapy Renal denervation procedure: catheter‐based renal denervation by applying low power radiofrequency to the renal artery using the OneShot system Follow‐up: up to 60 months
Outcomes	Major adverse event (MAE) rate through 30 days post‐randomisation Change in office SBP from baseline to 6 months Acute procedural safety Chronic procedural safety Reduction in SBP > 10 mmHg at 6 months Changes in office SBP and DBP from baseline to follow‐up visits
Starting date	September 2013
Contact information	Dierk Scheinert, MD Guiseppe Mancia, MD Universita Milano‐Bicocca, Ospedale San Gerardo di Monza
Notes

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RDNP‐2012‐01.

Study name	Renal denervation for resistant hypertension (RDNP‐2012‐01)
Methods	Study type: parallel‐group, RCT Country: Australia Setting: Hospital
Participants	Estimated number of patients: 100 Age: range 18 to 85 years SBP ≥ 140 mmHg or ≥ 130 mmHg for patients with diabetes (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) eGFR (mL/min/1.73 m²): ≥ 15 Exclusion criteria: pregnancy, unsuitable anatomy of renal arteries (diameter < 4 mm and length < 20 mm)
Interventions	Treatment group: renal denervation Control group: usual care Renal denervation procedure: catheter‐based renal denervation by applying low power radiofrequency to the renal artery using the Ardian Medtronic Symplicity catheter Follow‐up: up to 24 months
Outcomes	Percentage of patients achieving BP target (BP < 140/90 mmHg, or < 130/80 mmHg in diabetic patients) at 6 months post‐procedure Time to achieve BP target Change in markers of sympathetic nerve activity Change in left ventricular structure and function Change in quality of life Serum and urine biochemistry Change in markers of arterial stiffness
Starting date	February 2012
Contact information	Markus Schlaich, MD Baker IDI Heart & Diabetes Institute
Notes

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RENO.

Study name	Effect of renal denervation on no‐mediated sodium excretion and plasma levels of vasoactive hormones (RENO)
Methods	Study type: parallel‐group, RCT Country: Denmark Setting: Hospital
Participants	Estimated number of patients: 30 Age: range 30 to 70 years Office BP (mmHg): ≥ 145/75 eGFR (mL/min/1.73 m²): ≥ 45 Exclusion criteria: noncompliance, pregnancy, radiocontrast allergy, malignancy, congestive heart failure, unstable angina pectoris, previous myocardial infarction or PCI (< 6 mdr), secondary hypertension, renal artery stenosis or multiple renal arteries on CT, claudication
Interventions	Treatment group: renal denervation plus L‐NMMA treatment Control group: sham procedure plus L‐NMMA treatment Renal denervation procedure: catheter‐based renal denervation by applying low power radiofrequency to the renal artery using the Ardian Medtronic Simplicity catheter Follow‐up: up to 24 months
Outcomes	Fractional excretion of sodium after acute L‐NMMA treatment Glomerular filtration rate (GFR) before and after L‐NMMA treatment
Starting date	March 2012
Contact information	Esper N Bech, MD, Ph.D; jnbech@dadlnet.dk
Notes

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RENSYMPIS.

Study name	Renal sympathetic denervation and insulin sensitivity (RENSYMPIS study)
Methods	Study type: parallel‐group, RCT Country: Finland Setting: University
Participants	Estimated number of patients: 60 Age: range 30 to 69 years Office systolic BP (mmHg): ≥ 160 eGFR (mL/min/1.73 m²): ≥ 45 Exclusion criteria: secondary hypertension, pseudohypertension, pregnancy, significant stenotic valvular disease, oral anticoagulation, CCS III‐IV symptoms or CABG/PCI in the previous 6 months, prior stroke, contrast agent allergy, inappropriate renal artery anatomy (< 4 mm diameter, < 20 mm length)
Interventions	Treatment group: renal artery denervation Control group: optimisation of medical therapy Renal denervation procedure: catheter‐based renal denervation by applying low power radiofrequency to the renal artery using the Ardian Medtronic Simplicity catheter Follow‐up: up to 36 months
Outcomes	Office BP Ambulatory BP Insulin resistance Endothelial function
Starting date	January 2013
Contact information	Tuomas Paana, M.D; tuomas.paana@satshp.fi
Notes

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ReSET‐2.

Study name	Renal denervation in treatment resistant hypertension (ReSET‐2)
Methods	Study type: parallel‐group, RCT Country: Denmark Setting: University
Participants	Estimated number of patients: 70 Age: range 30 to 70 years Systolic daytime (24‐hour ambulatory blood pressure measurement) > 135 mmHg and < 145 mmHg eGFR (mL/min/1.73 m²): > 30 Exclusion criteria: pregnancy, noncompliance, heart failure (NYHA 3‐4), left ventricular ejection fraction < 50%, unstable coronary heart disease, coronary intervention within 6 months, myocardial infarction within 6 months, claudication, orthostatic syncope within 6 months, secondary hypertension, permanent atrial fibrillation, significant heart valve disease. Clinically significant abnormal electrolytes, haemoglobin, liver enzymes and TSH. Second and third degree heart block, macroscopic haematuria, proximal significant coronary stenosis, renal artery anatomy not suitable for renal ablation (stenosis, diameter < 4 mm, length < 20 mm, multiple renal arteries, severe calcifications). Moderate/severe obstructive sleep apnoea (AHI > 15) if on CPAP treatment
Interventions	Treatment group: renal denervation Control group: sham procedure Renal denervation procedure: catheter‐based renal denervation by applying low power radiofrequency to the renal artery using the EnligHTN catheter Follow‐up: up to 36 months
Outcomes	Change from baseline in daytime SBP Change from baseline in ABPM Change from baseline in central BP, augmentation index and pulse wave velocity Change from baseline in cold pressor response Change from baseline in intensity of medical antihypertensive therapy BP (clinic measurement) Renal function (eGFR and electrolytes)
Starting date	January 2013
Contact information	Henrik Vase, MD, PhD henvas@rm.dk Ole Mathiassen, MD, PhD onm@farm.au.dk
Notes

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RSD4CKD.

Study name	Renal sympathetic denervation in patients with chronic kidney disease and resistant hypertension (RSD4CKD)
Methods	Study type: parallel‐group, RCT Country: Japan Setting: University
Participants	Estimated number of patients: 100 Age: range 18 to 75 years eGFR (mL/min/1.73 m²): > 20 and < 70 Serum creatinine (mg/dL): 1.5‐5.0 Persistent proteinuria Resistant hypertension Nondiabetic renal disease Exclusion criteria: treatment with corticosteroids, nonsteroidal antiinflammatory or immunosuppressive drugs, connective‐tissue disease, obstructive uropathy, congestive heart failure (NYHA class III or IV), significant renovascular abnormalities (history of prior renal artery intervention, including balloon angioplasty or stenting; double renal artery on one side, distortion, and extension), measured by abdominal ultrasound or renal angiograms. History of myocardial infarction, unstable angina, cerebrovascular accident or alimentary tract haemorrhage in the previous 3 months, sick sinus syndrome, history of allergy to contrast media, psychiatric disorders, drug or alcohol abuse and pregnancy
Interventions	Treatment group: renal denervation + standard therapy Control group: standard therapy Renal denervation procedure: six to nine ablations at 10 W for 1 min each in both renal arteries Follow‐up: up to 36 months
Outcomes	All‐cause mortality Doubling of serum creatinine or end‐stage renal disease Urinary protein excretion and renal function Blood pressure Blood glucose Cardiac function and structure Arrhythmia Pulse wave velocity Quality of life Rehospitalisation rate Dialysis proportion
Starting date	November 2012
Contact information	Shan Qi jun; qjshan@njmu.edu.cn
Notes

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RSDARH.

Study name	Renal Sympathetic Denervation from the Adventitia on Resistant Hypertension (RSDARH）
Methods	Study type: parallel‐group, RCT Country: China Setting: University and hospital
Participants	Estimated number of patients: 126 Age: range 18 to 65 years Clinic SBP ≥ 140 mmHg or (and) DBP ≥ 90 mmHg, 24 hours dynamic blood pressure monitoring SBP ＞ 130 mmHg or (and) DBP ＞ 80 mmHg Estimated GFR (eGFR) ≥ 60 mL/min/1.73m² Exclusion criteria: secondary hypertension caused by any known cause; pregnant or planning to be pregnant; with renal artery diameter < 4 mm or length < 20 mm; patients with renal artery abnormalities. Acute myocardial infarction within six months, unstable angina or cerebrovascular disease; heart valve disease with significantly altered haemodynamics; other serious organic diseases
Interventions	Treatment group: Renal sympathetic denervation from the adventitia of renal artery and optimised medication regimen Control group: Optimised medication regimen Device: Radiofrequency ablation instruments Follow‐up: up to 6 months
Outcomes	Change in types and doses of antihypertensive medications in 1, 3, 6, 12 months after discharge Change in 24‐hour average diastolic blood pressure, daytime and night‐time systolic/diastolic blood pressure by ABPM in 6 months after discharge Change in 24‐hour average blood pressure, daytime and night‐time systolic/diastolic blood pressure by ABPM in 1, 3, 12 months after discharge Change in office systolic/diastolic blood pressure in 1, 3, 6, 12 months after discharge Change in systolic/diastolic blood pressure by home blood pressure monitoring in 1, 3, 6, 12 months after discharge Renal function in 1, 3, 6, 12 months after discharge The surgical complications of renal artery perforation, such as stenosis, and dissection associated with radiofrequency surgery Major cardiovascular and cerebrovascular events, including cardiac death, stroke and nonfatal myocardial infarction
Starting date	October 2018
Contact information	Chuanyu Gao, Dr +86 13937165590 gaocy6802@163.com
Notes

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RSDforAF.

Study name	Renal sympathetic denervation in patients with drug‐resistant hypertension and symptomatic atrial fibrillation (RSDforAF)
Methods	Study type: parallel‐group, RCT Country: China Setting: Hospital
Participants	Estimated number of patients: 200 Age: range 18 to 75 years Office SPB ≥ 160 mmHg (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) Baseline average systolic AMBP ≥ 135 mmHg eGFR (mL/min/1.73 m²): ≥ 45 Paroxysmal and persistent AF Exclusion criteria: pregnancy, type 1 diabetes mellitus, chronic oxygen support or mechanical ventilation, primary pulmonary hypertension, white‐coat hypertension, previous renal denervation, secondary hypertension, significant renovascular abnormalities, myocardial infarction, unstable angina pectoris or cerebrovascular accident < 180 days prior to enrolment. Blood clotting abnormalities, life expectancy < 12 months, renal arteries < 4 mm in diameter or < 20 mm in length or multiple renal arteries where the main renal arteries supply < 75% of the kidney. Pheochromocytoma, Cushing's disease, coarctation of the aorta, severely enlarged left atria ≥ 55 mm, sick sinus syndrome, reversible causes of AF
Interventions	Treatment group: renal denervation + drugs + cardioversion Control group: drugs Renal denervation procedure: four to eight ablations at 10 W for 60 seconds each in both renal arteries. In patients with persistent AF, direct‐current cardioversion performed immediately after renal sympathetic denervation Follow‐up: up to 36 months
Outcomes	Change in atrial fibrillation burden Rate controlling in persistent AF patients Office SBP Changes in cardiac structure and function Fasting blood glucose Glycated haemoglobin Blood lipids Apnoea‐hypopnoea index Pulse wave velocity Quality of life
Starting date	July 2012
Contact information	Qijun Shan; qjshan@40njmu.edu.cn
Notes

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SYMPLICITY HTN‐4.

Study name	Renal denervation in patients with uncontrolled hypertension (SYMPLICITY HTN‐4)
Methods	Study type: parallel‐group, RCT Country: USA Setting: University
Participants	Estimated number of patients: 44 Age: range 18 to 80 years eGFR (mL/min/1.73 m²): > 30 Office SBP > 140 mmHg and < 160 mmHg (despite stable medication regimen including 3 or more antihypertensive medications of different classes, including a diuretic) ABPM average SBP > 135 mmHg Exclusion criteria: pregnancy, inappropriate renal artery anatomy, type 1 diabetes mellitus, one or more episodes of orthostatic hypotension, chronic oxygen other than nocturnal respiratory support for sleep apnoea, primary pulmonary hypertension, previous organ transplant
Interventions	Treatment group: renal denervation Control group: sham procedure Renal denervation procedure: ablations done with the SYMPLICITY system Follow‐up: up to 24 months
Outcomes	Reaching BP goal Incidence of major adverse events through 1‐month post‐procedure Renal artery stenosis measured at 6 months
Starting date	October 2013
Contact information	David Kandzari, MD Piedmont Heart Institute
Notes

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^{AAA: abdominal aortic aneurysm} ^{ABPM: ambulatory blood pressure monitoring} ^{AHI: apnea hypopnea index} ^{BMI: body mass index} ^{BP: blood pressure} ^{BUN: blood urea nitrogen} ^{CABG: Coronary artery bypass graft surgery} ^{CPAP: continuos positive airway pressure} ^{CT: calcitonin} ^{CTA: computed tomography angiography} ^{DBP: diastolic blood pressure} ^{eGFR: estimated glomerular filtration rate} ^{EQ‐5D: euroQOL five‐dimension} ^{ESRD: end‐stage renal disease} ^{HFS: high ‐frequency stimulation} ^{HOMA: Homeostasis model assessment} ^{ICD: implantable cardioverter defibrillator} ^{L‐NMMA: Nitric Oxide Synthase Inhibitor NG‐Monomethyl‐L‐Arginine} ^{MACR: microalbumin to creatinine ratio} ^{MAE: major adverse events} ^{MDRD: Modification of Diet in Renal Disease}

^{MI: myocardial infarction} ^{MRA: magnetic resonance angiography} ^{MRCI: hypertensive medication complexity index} ^{NYHA: New York Heart Association} ^{PCI:percutaneous coronary intervention} ^{RCT: randomized clinical trial} ^{RD: renal denervation} ^{RF: radiofrequency} ^{RFA: radiofrequency ablation} ^{SBP: systolic blood pressure} ^{UACR: urinary albumin creatinine ratio} ^{W: wave} 

Differences between protocol and review

Authors order and contribution was updated after finalising the last revision of the review to best reflect individual contributions to this new version.

Contributions of authors

Drafting the protocol: GC, DB, AP, ER
Study selection: AL, LFI
Extracting data from studies: AL, LFI
Entering data into Review Manager: AP, LFI, DB
Carrying out the analysis: DB, AP
Interpreting the analysis: DB, AP, GC
Drafting the final review: DB, GC, AP, ER
Resolution of disagreements: AP, DB
Updating the review: DB, AP, GC, AL, LFI, ER

Sources of support

Internal sources

No sources of support, Other

N/A

External sources

No sources of support, Other

N/A

Declarations of interest

DB: in 2012, received an Honorary Fellowship from the Cochrane Renal Group as Fellow of the European Renal Best Practice (ERBP) group

AP: None known

GC: None known

AL: None known

LFI: None known

ER: None known

New search for studies and content updated (conclusions changed)

References

References to studies included in this review

DENER‐HTN 2015 {published data only}

Azizi M, Sapoval M, Gosse P, Monge M, Bobrie G, Delsart P, et al. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENER-HTN): a multicentre, open-label, randomised controlled trial. Lancet 2015;385(9981):1957-65. [DOI] [PubMed] [Google Scholar]
Forni O, Pereira V, Sapoval E, Azizi M. Prevalence and risk factors for refractory hypertension in the DENER-HTN study. Journal of Hypertension 2015;33:e51. [Google Scholar]
NCT01570777. Renal denervation in hypertension [Renal denervation in patients with resistant hypertension ]. clinicaltrials.gov/show/NCT01570777 (first received 2 April 2012).
Sapoval MR, Monge M, Pereira H, Azizi M. DENER-HTN trial: a prospective randomized control trial of the efficacy of renal artery denervation in resistant hypertension. Cardiovascular and Interventional Radiology 2014;1:S341. [Google Scholar]

DENERVHTA {published data only}

De La Sierra A, Pareja J, Armario P, Barrera A, Sans L, Vazquez S, et al. Renal denervation versus spironolactone in resistant hypertension. effects on circadian patterns and blood pressure variability. Journal of Hypertension 2016;34(Suppl 2):e43. [DOI] [PubMed] [Google Scholar]
De la Sierra A, Pareja J, Armario P, Barrera A, Yun S, Vazquez S, et al. Renal denervation vs. spironolactone in resistant hypertension: effects on circadian patterns and blood pressure variability. American Journal of Hypertension 2017;30:37-41. [DOI] [PubMed] [Google Scholar]
NCT02039492. Sympathetic renal denervation versus increment of pharmacological treatment in resistant arterial hypertension [Sympathetic renal denervation versus increment of pharmacological treatment in resistant arterial hypertension]. clinicaltrials.gov/show/NCT02039492 (first received 2012).
Oliveras A, Armario P, Clara A, Sans-Atxer L, Vazquez S, Pascual J, et al. Spironolactone versus sympathetic renal denervation to treat true resistant hypertension: results from the DENERVHTA study: a randomized controlled trial. Journal of Hypertension 2016;34:1863–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
Oliveras A, Armario P, Sans L, Clara A, Vazquez S, Molina L, et al. Organ damage changes in patients with resistant hypertension randomized to renal denervation or spironolactone: the DENERVHTA (Denervacion en Hipertension Arterial) study. Journal of Clinical Hypertension 2018;20(1):69-75. [DOI] [PMC free article] [PubMed] [Google Scholar]
Oliveras A, Armario P, Sans L, Clara A, Vazquez S, Molina L, et al. Preclinical target organ damage changes in patients with resistant hypertension randomized to renal denervation or spironolactone as add-on therapy. results from the DENERVHTA study. Hypertension 2016;68(Suppl 1):10. [Google Scholar]
Oliveras A, Armario P, Sans L, Clara A, Vazquez S, Molina LL, et al. Changes in subclinical organ damage in patients with resistant hypertension randomized to receive renal denervation or spironolactone as add-on therapy.the Denervhta study results. Journal of Hypertension 2016;34(Suppl 2):e47. [Google Scholar]

Desch 2015 {published data only}

Desch S, Okon T, Heinemann D, Kulle K, Rohnert K, Sonnabend M, et al. Randomized sham-controlled trial of renal sympathetic denervation in mild resistant hypertension. Hypertension 2015;65:1202-8. [DOI] [PubMed] [Google Scholar]
Fengler K, Heinemann D, Okon T, Röhnert K, Stiermaier T, Von Röder M, et al. Renal denervation improves exercise blood pressure: insights from a randomized, sham-controlled trial. Clinical Research in Cardiology 2016;105(7):592–600. [DOI: 10.1007/s00392-015-0955-8] [DOI] [PubMed] [Google Scholar]
NCT01656096. Renal sympathetic denervation in mild refractory hypertension [Renal sympathetic denervation in patients with mild refractory hypertension]. clinicaltrials.gov/show/NCT01656096 (first received 31 July 2012).

Franzen 2012 {published data only}

Franzen KF, Mortensen K, Himmel F, Stritzke J, Koester J, Bock J, et al. Percutaneous renal denervation (PRD) improves central hemodynamics and arterial stiffness - a pilot study. European Heart Journal 2012;33:771. [DOI] [PMC free article] [PubMed] [Google Scholar]

HTN‐JAPAN 2015 {published data only}

Kario K, Bakris G, Bhatt LD. Preferential reduction in morning/nocturnal hypertension by renal denervation for drug-resistant hypertension: a new ABPM analysis of SYMPLICITY HTN-3 and HTN-Japan. Journal of Hypertension 2015;33(Suppl 1):e52. [DOI: 10.1097/01.hjh.0000467484.20438.39] [DOI] [Google Scholar]
Kario K, Bhatt DL, Brar S, Cohen SA, Fahy M, Bakris GL. Effect of catheter-based renal denervation on morning and nocturnal blood pressure: insights from SYMPLICITY HTN-3 and SYMPLICITY HTN-Japan. Hypertension 2015;66:1130-7. [EMBASE: 10.1161/HYPERTENSIONAHA.115.06260] [DOI] [PubMed] [Google Scholar]
Kario K, Ogawa H, Okumura K, Okura T, Saito S, Ueno T, et al. SYMPLICITY HTN-Japan - First randomized controlled trial of catheter-based renal denervation in Asian patients. Circulation Journal 2015;79:1222-9. [DOI] [PubMed] [Google Scholar]
NCT01644604. Renal denervation by MDT-2211 system in patients with uncontrolled hypertension [The clinical study of renal denervation by MDT-2211 system in patients with uncontrolled hypertension]. clinicaltrials.gov/show/NCT01644604 (first received 29 June 2012).

INSPIRED {published data only}

Jacobs L, Persu A, Huang QF, Lengele JP, Thijs L, Hammer F, et al. Results of a randomized controlled pilot trial of intravascular renal denervation for management of treatment-resistant hypertension. Blood Pressure 2017;26(6):321-31. [DOI] [PubMed] [Google Scholar]
Jin Y, Jacobs L, Baelen M, Thijs L, Renkin J, Hammer F, et al. Rationale and design of the investigator-steered project on intravascular renal denervation for management of drug-resistant hypertension (INSPiRED) trial. Blood Pressure 2014;23:138-46. [DOI] [PMC free article] [PubMed] [Google Scholar]
Jin Y, Jocobs L, Hammer F, Renkin J, Persu A, Staessen JA. Rationale and design of the investigator-steered project on intravascular renal denervation for management of drug-resistant hypertension (INSPiRED) trial. Journal of the American Society of Hypertension 2014;8(S4):e71. [DOI] [PMC free article] [PubMed] [Google Scholar]
NCT01505010. Renal denervation for management of drug-resistant hypertension [Investigator-steered project on intravascular renal denervation for management of drug-resistant hypertension ]. clinicaltrials.gov/show/NCT01505010 (first received 2012). [DOI] [PMC free article] [PubMed]

Moiseeva 2020‐B {published data only}

Moiseeva A, Caraus A, Moscalu V, Calenici O, Ciobanu N, Sapojnic N, et al. The influence of renal denervation treatment on blood pressure in patients with resistant hypertension. European Journal of Preventive Cardiology 2020;26:P711. [Google Scholar]
Moiseeva A, Caraus A, Ciobanu N, Moscalu V, Surev A, Abras M, et al. The effects of renal artery denervation on blood pressure values and diastolic dysfunction in resistant hypertension. European Journal of Preventive Cardiology 2019;26(Suppl 1):S164-5. [Google Scholar]

Moiseeva 2020‐M {published data only}

Moiseeva A, Caraus A, Moscalu V, Calenici O, Ciobanu N, Sapojnic N, et al. The influence of renal denervation treatment on blood pressure in patients with resistant hypertension. European Journal of Preventive Cardiology 2020;27(1 Suppl 1):P711. [Google Scholar]
Moiseeva A, Caraus A, Ciobanu N Moscalu V, Surev A, Abras M, et al. The effects of renal artery denervation on blood pressure values and diastolic dysfunction in resistant hypertension. European Journal of Preventive Cardiology 2019;26(Suppl 1):S164-5. [Google Scholar]

Oslo RDN 2014 {published data only}

Bergland OU , Søraas CL , Larstorp ACK, Halvorsen LV, Hjørnholm U, Hoffman P, et al. The randomised Oslo study of renal denervation vs. antihypertensive drug adjustments: efficacy and safety through 7 years of follow-up. Blood Pressure 2020;30:41-50. [DOI] [PubMed] [Google Scholar]
Bergo KK, Larstorp AC, Hoffmann P, Hjørnholm U, Cataliotti A, Høieggen A, et al. Renal sympathetic denervation lowers systemic vascular resistance in true treatment-resistant hypertension. Blood pressure 2020;30:31-40. [DOI] [PubMed] [Google Scholar]
Elmula MF, Hoffmann P, Larstorp AC, Brekke M, Fossum E, Stenehjem A, et al. Renal sympathetic denervation is inferior to adjusted drug treatment in patients with true treatment resistant hypertension, a randomized controlled trial. European Heart Journal 2014;35:718. [Google Scholar]
Elmula MF, Hoffmann P, Larstorp AC, Fossum E, Brekke M, Kjeldsen SE, et al. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension 2014;63:991-9. [DOI] [PubMed] [Google Scholar]
Elmula MF, Hoffmann P, Larstorp AC, Hoieggen A, Kjeldsen S. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment resistant hypertension, a randomized clinical trial. Journal of the American College of Cardiology 2014;1:A1306. [DOI] [PubMed] [Google Scholar]
Elmula MF, Larstorp AC, Hoffmann P, Rostrup M, Hoieggen A, Kjeldsen S. One-year outcomes of a randomized study in renal denervation: Results for Oslo-RDN study. European Heart Journal 2016;37(Suppl 1):1056-7. [Google Scholar]
Larstorp BK, Hoieggen ACK, Hjornholm A, Rostrup P, Elmula MF. Haemodynamic changes in patients with treatment-resistant hypertension after renal sympathetic denervation compared to individualized drug therapy. Journal of hypertension 2016;34(Suppl 2):e305. [Google Scholar]
NCT01673516. Effect of renal sympathetic denervation on resistant hypertension and cardiovascular hemodynamic in comparison to intensive medical therapy utilizing impedance cardiography [Effect of renal sympathetic denervation on resistant hypertension and cardiovascular hemodynamic in comparison to intensive medical therapy utilizing impedance cardiography]. clinicaltrials.gov/show/NCT01673516 (first received 17 August 2012).
Soeraas CL, Bergland O, Halvorsen LV, Larstorp AC, Hjornholm U, Kjaer VN, et al. Long-term outcome of the randomized Oslo-RDN study. Journal of hypertension 2018;36 Suppl 1:e238-9. [Google Scholar]

Prague‐15 {published data only}

NCT01560312. Renal denervation in refractory hypertension [Renal denervation - hope for patients with refractory hypertension?]. clinicaltrials.gov/show/NCT01560312 (first received 16 May 2011).
Rosa J, Widimsky P, Tousek P, Petrak O, Curila K, Waldauf P, et al. Randomized comparison of renal denervation versus intensified pharmacotherapy including spironolactone in true-resistant hypertension: six-month results from the Prague-15 study. Hypertension 2015;65:407-13. [DOI] [PubMed] [Google Scholar]
Rosa J, Widimsky P, Waldauf P, Lambert L, Zelinka T, Taborsky M, et al. Role of adding spironolactone and renal denervation in true resistant hypertension: one-year outcomes of randomized PRAGUE-15 study. Hypertension 2016;67:397-403. [DOI] [PubMed] [Google Scholar]
Rosa J, Widimsky P, Waldauf P, Lambert L, Zelinka T, Taborsky M, et al. The role of adding spironolactone and renal denervation in true resistant hypertension. One-year outcomes of randomized study. European Heart Journal 2016;37 Suppl 1:230. [DOI] [PubMed] [Google Scholar]
Rosa J, Widimsky P, Waldauf P, Zelinka T, Petrak O, Taborsky M, et al. Renal denervation in comparison to intensified pharmacotherapy in true resistant hypertension. Two-year outcomes of randomised PRAGUE-15 study. European Heart Journal 2017;38 Suppl 1:157. [DOI] [PubMed] [Google Scholar]
Rosa J, Widmsky P, Waldauf P, Zelinka T, Petak O, Taborsky M, et al. Renal denervation in comparison with intensified pharmacotherapy in true resistant hypertension: 2-year outcomes of randomized PRAGUE-15 study. Journal of Hypertension 2017;35:1093–9. [DOI] [PubMed] [Google Scholar]
Rosa J, Zelinka T, Petrak O, Strauch B, Somloova Z, Indra T, et al. Importance of thorough investigation of resistant hypertension before renal denervation: should compliance to treatment be evaluated systematically? Journal of Human Hypertension 2014;28:684-8. [DOI] [PubMed] [Google Scholar]
Tousek P, Widimsky J, Rosa J, Curila K, Branny M, Nykl I, et al. Catheter-based renal denervation versus intensified medical treatment in patients with resistant hypertension: rationale and design of a multicenter randomized study - PRAGUE-15. Cor et Vasa 2014;56:e235-9. [Google Scholar]

RELIEF 2012 {published data only}

Ahmed H, Neuzil P, Schejbalova M, Bejr M, Kralovec S, Reddy VY. Renal sympathetic denervation for the management of chronic hypertension (RELIEF): 40 patient analysis. Circulation 2012;1(126):A17520. [Google Scholar]
Ahmed H, Neuzil P, Schejbalova M, Bejr M, Kralovec S, Reddy VY. Renal sympathetic denervation for the management of chronic hypertension (RELIEF): an interim analysis. Heart Rhythm 2012;1:S469-70. [Google Scholar]
NCT01628172. Renal sympathetic denervation for the management of chronic hypertension [Renal sympathetic denervation for the management of chronic hypertension]. clinicaltrials.gov/show/NCT01628172 (first received 2012).

ReSET 2015 {published data only}

Engholm M, Bertelsen JB, Mathiassen ON, Botker HE, Vase H, Peters CD, et al . Effects of renal denervation on coronary flow reserve and forearm dilation capacity in patients with treatment-resistant hypertension. A randomized, double-blinded, sham-controlled clinical trial. International Journal of Cardiology 2018;250:29-34. [DOI] [PubMed] [Google Scholar]
Mathiassen O, Bech JN, Buus NH, Christensen KL, Vase H, Bertelsen JB, et al. Renal sympathetic denervation in treatment resistant essential hypertension. A sham-controlled, double-blinded randomized trial (ReSET trial). Journal of the American College of Cardiology 2015;66:B41. [Google Scholar]
Mathiassen ON, Vase H, Bech JN, Christensen KL, Buus NH, Schroeder AP, et al. Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial. Journal of Hypertension 2016;34:1639–47. [DOI] [PMC free article] [PubMed] [Google Scholar]
NCT01459900. Renal sympathectomy in treatment resistant essential hypertension: a sham controlled randomized trial [Renal sympathectomy in treatment resistant essential hypertension: a sham controlled randomized trial]. clinicaltrials.gov/show/NCT01459900 (first received 2011).
Peters CD, Mathiassen ON, Vase H, Norgaard BJ, Christensen KL, Schroeder AP, et al. The effect of renal denervation on arterial stiffness, central blood pressure and heart rate variability in treatment resistant essential hypertension: a substudy of a randomized sham-controlled double-blinded trial (the ReSET trial). Blood Pressure 2017;26:366-80. [DOI] [PubMed] [Google Scholar]

SYMPATHY {published data only}

Beus E, Jager RL, Beeftink MM, Sanders MF, Spiering W, Vonken EJ, et al. Salt intake and blood pressure response to percutaneous renal denervation in resistant hypertension. Journal of Clinical Hypertension 2017;19:1125-33. [DOI] [PMC free article] [PubMed] [Google Scholar]
Jager RL, Beus E, Beeftink MMA, Sanders MF, Vonken EJ, Voskuil M, et al. Impact of Medication Adherence on the Effect of Renal Denervation: The SYMPATHY Trial. Hypertension 2017;69(4):678-84. [DOI] [PubMed] [Google Scholar]
NCT01850901. Renal sympathetic denervation as a new treatment for therapy resistant hypertension [Renal sympathetic denervation as a new treatment for therapy resistant hypertension - a multicenter randomized controlled trial]. clinicaltrials.gov/show/NCT01850901 (first received 2013).
Vink EE, De Beus E, De Jager RL, Voskuil M, Spiering W, Vonken EJ, et al. The effect of renal denervation added to standard pharmacologic treatment versus standard pharmacologic treatment alone in patients with resistant hypertension: rationale and design of the SYMPATHY trial. American Heart Journal 2014;167:308-14.e3. [DOI] [PubMed] [Google Scholar]

SYMPLICITY HTN‐2 2010 {published data only}

Boehm M, Schlaich MP, Krum H, Schmieder RE, Sobotka P, Esler MD. One-year pooled outcomes following renal sympathetic denervation in patients with resistant hypertension: from the SYMPLICITY HTN-2 trial. European Heart Journal 2012;33:770. [Google Scholar]
Esler M, Krum H, Schmieder R, Bohm M. Renal sympathetic denervation for treatment of resistant hypertension: Two-year update from the SYMPLICITY HTN-2 randomized controlled trial. Journal of the American College of Cardiology 2013;1:E1386. [Google Scholar]
Esler MD, Bohm M, Sievert H, Rump CL, Schmieder RE, Krum H, et al. Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36-month results from the SYMPLICITY HTN-2 randomized clinical trial. European Heart Journal 2014;35:1752-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
Esler MD, Krum H, Schlaich M, et al. Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the SYMPLICITY HTN-2 randomized, controlled trial. Orvosi Hetilap 2014;155(21):843. [DOI: 10.1556/OH.2014.21M] [DOI] [PubMed] [Google Scholar]
Esler MD, Krum H, Schlaich M, Schmieder R, Bohm M, Sobotka P. Renal sympathetic denervation for treatment of resistant hypertension: One year results from the SYMPLICITY HTN-2 randomized controlled trial. Journal of the American College of Cardiology 2012;1:E1705. [DOI] [PubMed] [Google Scholar]
Esler MD, Krum H, Schlaich M, Schmieder RE, Bohm M, Sobotka PA, et al. Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the SYMLICITY HTN-2 randomized, controlled trial. Circulation 2012;126:2976-82. [DOI] [PubMed] [Google Scholar]
Esler MD, Krum H, Schlaich M, Schmieder RE, Bohm M, Sobotka PA, et al. SYMPLICITY HTN-2: international, multicenter, prospective, randomized, controlled trial of endovascular selective renal sympathetic denervation for the treatment of hypertension. Circulation 2010;122:2220. [DOI] [PubMed] [Google Scholar]
Esler MD, Krum H, Schlaich MP, Schmieder RE, Boehm M, Sobotka P. Catheter-based renal sympathetic denervation in patients with resistant hypertension: 18-month follow-up of the SYMPLICITY HTN-2 trial. European Heart Journal 2012;33:181. [Google Scholar]
Esler MD, Krum H, Schlaich MP, Schmieder RE, Bohm M. Persistent and safe blood pressure lowering effects of renal artery denervation: three-year follow-up from the SYMPLICITY HTN-2 trial. Journal of the American College of Cardiology 2013;1:B19. [Google Scholar]
Murray E, Henry K, Marcus S, Roland S, Michael B. Long-term follow-up of catheter-based renal denervation in patients with treatment resistant hypertension: the SYMPLICITY HTN-2 trial. Journal of Clinical Hypertension 2013;15(Suppl 1):28. [Google Scholar]
NCT00888433. Renal denervation in patients with uncontrolled hypertension (SYMPLICITY HTN-2) [Renal denervation in patients with uncontrolled hypertension (SYMPLICITY HTN-2)]. clinicaltrials.gov/show//NCT00888433 (first received 2009).
Symplicity HTN-2 Investigators, Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (the SYMPLICITY HTN-2 Trial): a randomised controlled trial. Lancet 2010;376(9756):1903-9. [DOI: 10.1016/S0140-6736(10)62039-9] [DOI] [PubMed] [Google Scholar]
Ukena C, Mahfoud F, Ewen S, Kindermann I, Boehm M. Cardiorespiratory response to exercise after renal sympathetic denervation in resistant hypertension. Cardiology (Switzerland) 2013;125:158. [DOI] [PubMed] [Google Scholar]
Ukena C, Mahfoud F, Kindermann I, Barth C, Lenski M, Kindermann M, et al. Cardiorespiratory response to exercise after renal sympathetic denervation in patients with resistant hypertension. Journal of the American College of Cardiology 2011;58:1176-82. [DOI] [PubMed] [Google Scholar]
Ukena C, Mahfoud F, Kindermann I, Kindermann M, Brandt MC, Hoppe U, et al. Cardiorespiratory response to exercise after renal sympathetic denervation in patients with resistant hypertension. European Heart Journal 2011;32:960. [DOI] [PubMed] [Google Scholar]

SYMPLICITY HTN‐3 2014 {published data only}

Bakris GL, Townsend RR, Flack JM, Brar S, Cohen SA, D'Agostino, et al. 12-month blood pressure results of catheter-based renal artery denervation for resistant hypertension: the SYMPLICITY HTN-3 trial. Journal of the American College of Cardiology 2015;65:1314-21. [DOI] [PubMed] [Google Scholar]
Bakris GL, Townsend RR, Liu M, Cohen SA, D'Agostino R, Flack JM, et al. Impact of renal denervation on 24-hour ambulatory blood pressure: results from SYMPLICITY HTN-3. Journal of the American College of Cardiology 2014;64:1071-8. [DOI] [PubMed] [Google Scholar]
Bhatt DL, Bakris GL. Long-term (24-month) blood pressure results of catheter-based renal artery denervation: SYMPLICITY HTN-3 randomized controlled trial. Journal of the American College of Cardiology 2015;1:B38-9. [DOI] [PubMed] [Google Scholar]
Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, et al. A controlled trial of renal denervation for resistant hypertension. New England Journal of Medicine 2014;370:1393-401. [DOI] [PubMed] [Google Scholar]
Bhatt DL, Kandzari DE, O'Neill WW. A controlled trial of renal denervation for resistant hypertension. Journal of Vascular Surgery 2014;60:266. [DOI] [PubMed] [Google Scholar]
Divison JA, Escobar CC, Segui DM. Controlled clinical trial on renal denervation in resistant hypertension. Semergen 2014;40:345-6. [DOI] [PubMed] [Google Scholar]
Flack J, Bakris GL, Kandzari D, Katzen BT, Leon M, Mauri L, et al. SYMPLICITY HTN-3: outcomes in the African-American and Non-African American populations. Journal of the American College of Cardiology 2014;1:B119-20. [Google Scholar]
Flack JM, Bhatt DL, Kandzari DE, Brown D, Brar S, Choi J, et al. An analysis of the blood pressure and safety outcomes to renal denervation in African Americans and Non-African Americans in the SYMPLICITY HTN-3 trial. Journal of the American Society of Hypertension 2015;9:769-79. [DOI] [PubMed] [Google Scholar]
Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M, et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. European Heart Journal 2015;36:219-27. [DOI] [PMC free article] [PubMed] [Google Scholar]
Kandzari DE, Bhatt DL, Sobotka PA, O'Neill WW, Esler M, Flack JM, et al. Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 trial. Clinical Cardiology 2012;35:528-35. [DOI] [PMC free article] [PubMed] [Google Scholar]
Kario K, Bakris G, Pocock S, Fahy M, Bhatt DL. Changes in nocturnal blood pressure post-renal denervation: comparison of treatment versus control groups in SYMPLICITY HTN-3. European Heart Journal 2019;40 Suppl 1:664. [Google Scholar]
Kario K, Bakris GL, Bhatt D. Preferential reduction in morning/nocturnal hypertension by renal denervation for drug-resistant hypertension: a new ABPM analysis of SYMPLICITY HTN-3 and HTN-Japan. Journal of Hypertension 2015;33 Suppl 1:e52. [Google Scholar]
Kario K, Bhatt DL, Brar S, Cohen SA, Fahy M, Bakris GL. Effect of catheter-based renal denervation on morning and nocturnal blood pressure: insights from SYMPLICITY HTN-3 and SYMPLICITY HTN-Japan. Hypertension 2015;66:1130-7. [DOI] [PubMed] [Google Scholar]
Kario K, Bhatt DL, Townsend R, Flack J, Negoita M, Oparil S, et al. Potential reduction in office and nocturnal blood pressure after renal denervation in patients with obstructive sleep apnea: A subgroup analysis of SYMPLICITY HTN-3. European Heart Journal 2015;36:186. [Google Scholar]
NCT01418261. SYMPLICITY HTN-3 renal denervation in patients with uncontrolled hypertension [Renal denervation in patients with uncontrolled hypertension (SYMPLICITY HTN-3)]. clinicaltrials.gov/show/NCT01418261 (first received 2011).
Pekarskiy S, Baev A, Mordovin V, Sitkova E, Semke G, Ripp T, et al. Failure of renal denervation in SYMPLICITY HTN-3 is a predictable result of anatomically inadequate operative technique and not the true limitations of the technology. Journal of Hypertension 2015;33 Suppl 1:e108. [Google Scholar]

Warchol 2014 {published data only}

NCT01366625. Renal denervation in patients with resistant hypertension and obstructive sleep apnea [Effects of renal denervation on blood pressure and clinical course of obstructive sleep apnea in patients with resistant hypertension]. clinicaltrials.gov/show/NCT01366625 (first received 2011).
Warchol-Celinska E, Prejbisz A, Kadziela J, Florczak E, Januszewicz M, Michalowska I, et al. Renal Denervation in Resistant Hypertension and Obstructive Sleep Apnea: Randomized Proof-of-Concept Phase II Trial. Hypertension 2018;72:381-90. [DOI] [PubMed] [Google Scholar]
Warchol-Celinska E, Prejbisz A, Kadziela J, Sliwinski P, Plywaczewski R, Florczak E, et al. Effect of renal denervation on blood pressure levels and clinical course of obstructive sleep apnea in patients with resistant hypertension-3 months outcomes of randomized trial. European Heart Journal 2016;37 Suppl 1:793. [Google Scholar]
Warchol E, Prejbisz A, Kadziela J, Florczak E, Kabat M, Sliwinski P, et al. The impact of renal sympathetic denervation on office and ambulatory blood pressure levels in patients with true resistant hypertension and obstructive sleep apnea: the interim analysis. European Heart Journal 2014;35:231. [Google Scholar]

References to studies excluded from this review

Ahmed 2012b {published data only}

Ahmed H, Neuzil P, Skoda J, Petru J, Sediva L, Schejbalova M, et al. Renal sympathetic denervation using an irrigated radiofrequency ablation catheter for the management of drug-resistant hypertension. JACC. Cardiovascular Interventions 2012;5:758-65. [DOI] [PubMed] [Google Scholar]

Ahmed 2013 {published data only}

Ahmed H, Miller MA, Dukkipati SR, Cammack S, Koruth JS, Gangireddy S, et al. Adjunctive renal sympathetic denervation to modify hypertension as upstream therapy in the treatment of atrial fibrillation (H-FIB) study: clinical background and study design. Journal of Cardiovascular Electrophysiology 2013;24:503-9. [DOI] [PubMed] [Google Scholar]

Azizi 2018 {published data only}

Azizi M, Schmieder RE, Mahfoud F, Weber M, Daemen J, Davies J, et al. Radiance-HTN solo: A multicenter, randomized, shamcontrolled study of renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications. Journal of Hypertension 2018;36 Suppl 1:e238. [Google Scholar]

Azizi 2019 {published data only}

Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Lobo MD, et al. Six-month results of treatment-blinded medication titration for hypertension control following randomization to endovascular ultrasound renal denervation or a sham procedure in the RADIANCE-HTN SOLO trial. Circulation 2019;139:2542-2553. [DOI: 10.1161/CIRCULATIONAHA.119.040451] [DOI] [PubMed] [Google Scholar]

Azizi M 2019 {published data only}

Azizi M, Schmieder R, Mahfoud F, Weber M, Daemen J, Lobo M, et al. Treatment-Blinded Medication Titration for Hypertension Control Following Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure. Journal of the American College of Cardiology 2019;73(9 Suppl 1):1034. [DOI] [PubMed] [Google Scholar]

Baev 2017 {published data only}

Baev A, Pekarskiy S, Mordovin V, Ripp T, Falkovskaya A, Lichikaki V, et al. A distal mode of renal denervation in segmental branches of renal artery versus conventional main trunk therapy: a double blind randomized controlled study in patients with resistant hypertension. Journal of the american college of cardiology 2017;18 Suppl 1:B86. [Google Scholar]

Bohm 2018 {published data only}

Bohm M, Kandzari D, Townsend R, Mahfoud F, Weber M, Fahy M, et al. Spyral HTN-OFF MED trial: Changes in office and ambulatory heart rate. Journal of Hypertension 2018;36 Suppl 1:e23-e24. [Google Scholar]

Bohm 2019 {published data only}

Bohm M, Mahfoud F, Townsend RR, Kandzari DE, Pocock S, Ukena C, et al. Ambulatory heart rate reduction after catheter-based renal denervation in hypertensive patients not receiving anti-hypertensive medications: data from SPYRAL HTN-OFF MED, a randomized, sham-controlled, proof-of-concept trial. European Heart Journal 2019;40(9):743-51. [DOI] [PubMed] [Google Scholar]

Bohm 2020 {published data only}

Bohm M, Townsend RR, Kario K, Kandzari D, Mahfoud F, Weber MA, et al. Correction to: rationale and design of two randomized sham controlled of catheterbased renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTNOFF MED Pivotal) and presence (SPYRAL HTNON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design. Clinical Research in Cardiology 2020;109:653. [DOI] [PMC free article] [PubMed] [Google Scholar]

Bohm 2020b {published data only}

Bohm M, Townsend RR, Kario K, Kandzari D, Mahfoud F, Weber MA, et al. Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design. Clinical Research in Cardiology 2020;109:289-302. [DOI: 10.1007/s00392-020-01595-z] [DOI] [PMC free article] [PubMed] [Google Scholar]

Bohm 2020c {published data only}

Bohm M, Kario K, Kandzari DE, Mahfoud F, Weber MA, Schmieder RE, et al T. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet 2020;395:1444-51. [DOI: 10.1016/S0140-6736(20)30554-7] [DOI] [PubMed] [Google Scholar]

Bosch 2020 {published data only}

Bosch A, Schmid A, Ott C, Kannenkeril D, Karg MV, Ditting T, et al. Copeptin levels in patients with treatment-resistant hypertension before and 6 months after renal denervation. American Journal of Hypertension 2020;33(2):182-9. [DOI: 10.1093/ajh/hpz155] [DOI] [PubMed] [Google Scholar]

Brandt 2012 {published data only}

Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M, et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. Journal of the American College of Cardiology 2012;59:901-9. [DOI] [PubMed] [Google Scholar]

Brandt 2012a {published data only}

Brandt MC, Reda S, Mahfoud F, Lenski M, Bohm M, Hoppe UC. Effects of renal sympathetic denervation on arterial stiffness and central hemodynamics in patients with resistant hypertension. Journal of the American College of Cardiology 2012;60:1956-65. [DOI] [PubMed] [Google Scholar]

Chen 2017 {published data only}

Chen S, Kiuchi MG, Acou WJ, Derndorfer M, Wang J, Li R, et al. Feasibility of catheter ablation renal denervation in "mild" resistant hypertension. Journal of Clinical Hypertension 2017;19(4):361-8. [DOI] [PMC free article] [PubMed] [Google Scholar]

Chen 2019 {published data only}

Chen H, Ji M, Zhang Y, Xu Y, Qiao L, Shen L, et al. Correction to: efficiency and safety of renal denervation via cryoablation (Cryo-RDN) in Chinese patients with uncontrolled hypertension: study protocol for a randomized controlled trial. Trials 2019;20:770. [DOI] [PMC free article] [PubMed] [Google Scholar]

Chen 2019b {published data only}

Chen H, Ji M, Zhang Y, Xu Y, Qiao L, Shen L, et al. Efficiency and safety of renal denervation via cryoablation (Cryo-RDN) in Chinese patients with uncontrolled hypertension: study protocol for a randomized controlled trial. Trials 2019;20:653. [DOI: 10.1186/s13063-019-3693-9] [DOI] [PMC free article] [PubMed] [Google Scholar]

ChiCTR‐ONC‐12002901 {published data only}

ChiCTR-ONC-12002901. Transcatheter renal denervation for patients with resistant hypertension [Transcatheter renal denervation for patients with resistant hypertension]. Http://www.chictr.org.cn/showproj.aspx? Proj=6653 2012.

ChiCTR‐ONC‐13003231 {published data only}

ChiCTR-ONC-13003231. Noninvasive renal sympathetic denervation by high-intensity focused ultrasound (HIFU) in patients with refractory hypertension [Noninvasive renal sympathetic denervation by high-intensity focused ultrasound (HIFU) in patients with refractory hypertension]. http://www.chictr.org.cn/showproj.aspx?proj=6328 2013.

ChiCTR‐TNC‐12002900 {published data only}

ChiCTR-TNC-12002900. A comprehensive assessment of the cardiovascular effects of transcatheter renal sympathetic nerve denervation [A comprehensive assessment of the cardiovascular effects of transcatheter renal sympathetic nerve denervation]. http://www.chictr.org.cn/showproj.aspx?proj=6654 2012.

Courand 2016 {published data only}

Courand PY, Pereira H, Gosse P, Bobrie G, Delsart P, Mounier-Vehier C, et al. Presence of aortic abdominal calcifications in patients with resistant hypertension and bp response in the renal denervation for hypertension (DENERHTN) trial. Journal of Hypertension 2016;34 Suppl 2:e172. [Google Scholar]

Courand 2017 {published data only}

Courand PY, Pereira H, Del Giudice C, Gosse P, Monge, MBobrie, G et al. Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial. Journal of the American Heart Association 2017;6(10):10. [DOI] [PMC free article] [PubMed] [Google Scholar]

de Jager, R. 2018 {published data only}

Jager RL, Van Maarseveen EM, Bots ML, Blankestijn PJ. Medication adherence in patients with apparent resistant hypertension: findings from the SYMPATHY trial. British Journal of Clinical Pharmacology 2018;84(1):18-24. [DOI] [PMC free article] [PubMed] [Google Scholar]

De Jager 2017 {published data only}

De Jager R, Van Maarseveen E, Bots M, Blankestijn P. Medication adherence in patients with apparent resistant hypertension: Findings from the sympathy trial. Nephrology Dialysis Transplantation 2017;32 Suppl 3:iii47. [DOI] [PMC free article] [PubMed] [Google Scholar]

Dimitriadis 2017 {published data only}

Dimitriadis K, Tsioufis K, Kasiakogias A, Kalos TH, Liatakis G, Nikolopoulou L, et al. Effects of multielectrode renal denervation on sympathetic nerve activity and insulin resistance in metabolic syndrome. Journal of Hypertension 2017;35 Suppl 2:e148. [DOI] [PubMed] [Google Scholar]

DRKS00005865 {published data only}

DRKS00005865. Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension. http://www.drks.de/DRKS00005865 2014.

DRKS00006405 {published data only}

DRKS00006405. Safety and efficacy study investigating the effects of catheter-based renal denervation on different organ systems in patients with increased sympathetic activity. http://www.drks.de/DRKS00006405 2014.

DRKS00006420 {published data only}

DRKS00006420. Rapid renal sympathetic denervation for resistant hypertension using the oneshot™ ablation system. http://www.drks.de/DRKS00006420 2014. [DOI] [PubMed]

DRKS00006493 {published data only}

DRKS00006493. A randomized safety and efficacy study investigating the effects of catheter-based renal denervation in patients after renal transplantation. http://www.drks.de/DRKS00006493 2015.

Eikelis 2017 {published data only}

Eikelis N, Hering D, Marusic P, Duval J, Hammond LJ, Walton AS, et al. The effect of renal denervation on plasma adipokine profile in patients with treatment resistant hypertension. Frontiers in Physiology 2017;8:369. [DOI] [PMC free article] [PubMed] [Google Scholar]

EnligHTN III {published data only}

NCT01836146. International first-in-human study of the EnligHTN generation 2 system in patients with drug-resistant uncontrolled hypertension (EnligHTN III). clinicaltrials.gov/show/NCT01836146 (first received 2013).

Esler 2013 {published data only}

Esler M, Krum H, Schlaich M, Bohm M, Schmieder RE. Renal denervation via catheter-based delivery of radiofrequency energy significantly reduces blood pressure in subjects with severe treatment-resistant hypertension: long-term results from the SYMPLICITY-HTN clinical trials. Circulation 2013;128(S22):A14747. [Google Scholar]

Ewen 2014 {published data only}

Ewen S, Mahfoud F, Linz D, Poss J, Cremers B, Kindermann I, et al. Effects of renal sympathetic denervation on exercise blood pressure, heart rate, and capacity in patients with resistant hypertension. Hypertension 2014;63:839-45. [DOI] [PubMed] [Google Scholar]

Fadl Elmula 2013 {published data only}

Elmula MF, Hoffmann P, Fossum E, Brekke M, Gjonnaess E, Hjornholm U, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension after witnessed intake of medication before qualifying ambulatory blood pressure. Hypertension 2013;62:526-32. [DOI] [PubMed] [Google Scholar]

Fengler 2018 {published data only}

Fengler K, Hollriegel R, Okon T, Stiermaier T, Rommel KP, Blazek S, et al. Ultrasound-based renal sympathetic denervation for the treatment of therapy-resistant hypertension: a single-center experience. Journal of Hypertension 2018;35(6):1310-7. [DOI] [PubMed] [Google Scholar]

Forssell 2020 {published data only}

Forssell C, Bjarnegard N, Nystrom FH. A pilot study of perioperative external circumferential cryoablation of human renal arteries for sympathetic denervation. Vascular specialist international 2020;36:151-7. [DOI: 10.5758/vsi.200023] [DOI] [PMC free article] [PubMed] [Google Scholar]

Grassi 2015 {published data only}

Grassi G, Seravalle G, Brambilla G, Trabattoni D, Cuspidi C, Corso R, et al. Blood pressure responses to renal denervation precede and are independent of the sympathetic and baroreflex effects. Hypertension 2015;65:1206-16. [DOI] [PubMed] [Google Scholar]

Hamdidouche 2019 {published data only}

Hamdidouche I, Gosse P, Cremer A, Lorthioir A, Delsart P, Courand PY, et al. Clinic versus ambulatory blood pressure in resistant hypertension: impact of antihypertensive medication nonadherence: a post hoc analysis the DENERHTN study. Hypertension 2019;74:1096-1103. [DOI: 10.1161/HYPERTENSIONAHA.119.13520] [DOI] [PubMed] [Google Scholar]

Hering 2013 {published data only}

Hering D, Lambert EA, Marusic P, Ika-Sari C, Walton AS, Krum H, et al. Renal nerve ablation reduces augmentation index in patients with resistant hypertension. Journal of Hypertension 2013;31:1893-900. [DOI] [PubMed] [Google Scholar]

Kampmann 2016 {published data only}

Kampmann U, Mathiassen ON, Christensen KL, Buus NH, Bjerre M, Moller N, et al. The effect of renal denervation on insulin sensitivity, blood pressure, and inflammatory markers in treatment-resistant hypertensive patients. Diabetes 2016;65 Suppl 1:A121. [DOI] [PMC free article] [PubMed] [Google Scholar]

Kandzari 2016 {published data only}

Kandzari DE, Kario K, Mahfoud F, Cohen SA, Pilcher G, Pocock S, et al. The SPYRAL-HTN global clinical trial program: rationale and design for studies of renal denervation in the absence (SPYRAL-HTN OFF-MED) and presence (SPYRAL-HTN ON-MED) of antihypertensive medications. American Heart Journal 2016;171:82-91. [DOI] [PubMed] [Google Scholar]

Kandzari 2018 {published data only}

Kandzari DE, Bohm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet 2018;391:2346-55. [DOI] [PubMed] [Google Scholar]

Karbasi‐Afshar 2013 {published data only}

Karbasi-Afshar R, Noroozian R, Shahmari A, Saburi A. The effect of renal arteries sympathectomy on refractory hypertension. Tehran University Medical Journal 2013;71:179-84. [Google Scholar]

Kario 2018 {published data only}

Kario K, Bohm M, Mahfoud F, Townsend RR, Weber MA, Patel M, et al. Twenty-four-hour ambulatory blood pressure reduction patterns after renal denervation in the SPYRAL HTN-OFF MED trial. Circulation 2018;138(15):1602-4. [DOI] [PubMed] [Google Scholar]

Kario 2019 {published data only}

Kario K, Yamamoto E, Tomita H, Okura T, Saito S, Ueno T, et al. Sufficient and persistent blood pressure reduction in the final long-term results from SYMPLICITY HTN-Japan - safety and efficacy of renal denervation at 3 years. Circulation Journal 2019;83(3):622-9. [DOI] [PubMed] [Google Scholar]

Kario 2020 {published data only}

Kario K, Weber MA, Bohm M, Townsend RR, Mahfoud F, Schmieder RE, et al. Effect of renal denervation in attenuating the stress of morning surge in blood pressure: post-hoc analysis from the SPYRAL HTN-ON MED trial. Clinical research in cardiology 2020;110(5):725-731. [DOI: 10.1007/s00392-020-01718-6] [DOI] [PubMed] [Google Scholar]

Kario K 2018 {published data only}

Kario K, Boehm M, Townsend R, Mahfoud F, Pocock S, Weber M, et al. Twenty-four-hour ambulatory blood pressure reduction profiles of renal denervation in the spyral HTN-OFF MED trial. Journal of the American College of Cardiology 2018;71(11 Suppl 1):no pagination. [Google Scholar]

Katholi 2014 {published data only}

Katholi R, Esler M, Krum H, Rocha-Singh K, Schlaich M, Bohm M, et al. Pooled 3-year SYMPLICITY HTN-1 and SYMPLICITY HTN-2 results and diabetes subgroup analysis. JACC: Cardiovascular Interventions 2014;1:S50. [Google Scholar]

Kjeldsen 2014 {published data only}

Kjeldsen SE, Narkiewicz K, Oparil S, Hedner T. Renal denervation in treatment-resistant hypertension: Oslo RDN, SYMPLICITY HTN-3 and INSPiRED randomized trials. Blood Pressure 2014;23:135-7. [DOI] [PubMed] [Google Scholar]

Krum 2014 {published data only}

Krum H, Schlaich MP, Sobotka PA, Bohm M, Mahfoud F, Rocha-Singh K, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the SYMPLICITY HTN-1 study. Lancet 2014;383:622-9 . [DOI] [PubMed] [Google Scholar]

Li 2019 {published data only}

Li Y, Nawabi AQ, Feng Y, Dai Q, Ma G, Liu N. Safety and efficacy of a new renal denervation catheter in hypertensive patients in the absent of antihypertensive medications: a pilot study. International Journal Of Hypertension 2019;2019:7929706. [DOI: 10.1155/2019/7929706] [DOI] [PMC free article] [PubMed] [Google Scholar]

Li 2019 {published data only}

Li LY, Lu TJ, Zhang H, Deng WM, Duan QX, Gao JQ, et al. Renal sympathetic denervation for treatment of resistant hypertension using a 5 F microtube-irrigated ablation catheter. Academic journal of second military medical university 2019;40:1263-9. [DOI: 10.16781/j.0258-879x.2019.11.1263] [DOI] [Google Scholar]

Lobo 2015 {published data only}

Lobo M, Saxena M, Jain A, Walters D, Pincus M, Montarello J, et al. Safety and performance of the EnligHTN renal denervation system in patients with uncontrolled hypertension and chronic kidney disease: 12 month results from the EnligHTN II study. Journal of Hypertension 2015;33(1):e363. [Google Scholar]

Lurz 2020 {published data only}

Lurz P, Kresoja KP, Rommel KP, Von Roeder M, Besler C, Lucke C, et al. Changes in stroke volume after renal denervation: insight from cardiac magnetic resonance imaging. Hypertension 2020;75:707-13. [DOI: 10.1161/HYPERTENSIONAHA.119.14310] [DOI] [PubMed] [Google Scholar]

Mahfoud 2011 {published data only}

Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, et al. Effect of renal sympathetic denervation on glucosmetabolism in patients with resistant hypertension. Internist 2011;52:36. [DOI] [PubMed] [Google Scholar]

Mahfoud 2011a {published data only}

Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation 2011;123:1940-6. [DOI] [PubMed] [Google Scholar]

Mahfoud 2012 {published data only}

Mahfoud F, Cremers B, Janker J, Link B, Vonend O, Ukena C, et al. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension 2012;60:419-24. [DOI] [PubMed] [Google Scholar]

Mahfoud 2013 {published data only}

Mahfoud F, Ukena C, Schmieder RE, Cremers B, Rump LC, Vonend O, et al. Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension. Circulation 2013;128(2):132-40. [DOI] [PubMed] [Google Scholar]

Mahfoud 2014 {published data only}

Mahfoud F, Urban D, Teller D, Linz D, Stawowy P, Hassel JH, et al. Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial. European Heart Journal 2014;35:2224-31b. [DOI] [PubMed] [Google Scholar]

Mahfoud 2019 {published data only}

Mahfoud F, Kandzari DE, Kario K, Pocock S, Schmieder RE, Townsend RR, et al. Changes in plasma renin activity after renal denervation in the SPYRAL HTN-off med trial. Hypertension 2019;74 Suppl 1:no pagination. [DOI: 10.1161/hyp.74.suppl_1.109] [DOI] [Google Scholar]

Mahfoud 2020 {published data only}

Mahfoud F, Renkin J, Sievert H, Bertog S, Ewen S, Bohm M, et al. Alcohol-mediated renal denervation using the peregrine system infusion catheter for treatment of hypertension. JACC: cardiovascular interventions 2020;13:471-84. [DOI: 10.1016/j.jcin.2019.10.048] [DOI] [PubMed] [Google Scholar]

Mahfoud 2020b {published data only}

Mahfoud F, Mancia G, Schmieder R, Narkiewicz K, Ruilope L, Schlaich M, et al. Renal denervation in high-risk patients with hypertension. Journal of the American College of Cardiology 2020;75(23):2879-88. [DOI] [PubMed] [Google Scholar]

Mahfoud 2020c {published data only}

Mahfoud F, Townsend R, Kandzari D, Kario K, Schmieder R, Tsioufis K, et al . TCT Connect-417 impact of renal denervation on plasma renin activity and relationship of baseline plasma renin activity to blood pressure lowering response to renal denervation in the SPYRAL HTN-OFF MED pivotal trial. Journal of the American College of Cardiology 2020;76 (17 Suppl ):B179. [Google Scholar]

NCT01117025 {published data only}

NCT01117025. Combined treatment of resistant hypertension and atrial fibrillation. clinicaltrials.gov/show/NCT01117025 (first received 2010).

NCT01465724 {published data only}

NCT01465724. Renal sympathetic denervation for treatment of metabolic syndrome associated hypertension (Metabolic Syndrome study). clinicaltrials.gov/show/NCT01465724 (first received 2013).

NCT01583881 {published data only}

NCT01583881. Renal denervation in patients with heart failure with normal LV ejection fraction. clinicaltrials.gov/show/NCT01583881 (first received 2014).

NCT01631370 {published data only}

NCT01631370. The effects of renal sympathetic denervation on insulin sensitivity in patients with resistant essential hypertension. clinicaltrials.gov/show/NCT01631370 (first received 2012).

NCT01635998 {published data only}

NCT01635998. Adjunctive renal sympathetic denervation to modify hypertension as upstream therapy in the treatment of atrial fibrillation. clinicaltrials.gov/show/NCT01635998 (first received 2012). [DOI] [PubMed]

NCT01687725 {published data only}

NCT01687725. Renal denervation in treatment resistant hypertension. clinicaltrials.gov/show/NCT01687725 (first received 2012).

NCT01733901 {published data only}

NCT01733901. Renal sympathetic denervation as secondary prevention for patients after percutaneous coronary intervention. clinicaltrials.gov/show/NCT01733901 (first received 2012).

NCT01814111 {published data only}

NCT01814111. Safety and effectiveness study of percutaneous catheter-based sympathetic denervation of the renal arteries in patients with hypertension and paroxysmal atrial fibrillation. clinicaltrials.gov/show/NCT01814111 (first received 2012).

NCT01848314 {published data only}

NCT01848314. The effect of renal denervation on renal flow in humans. clinicaltrials.gov/show/NCT01848314 (first received 2013).

NCT01873352 {published data only}

NCT01873352. Renal artery denervation in addition to catheter ablation to eliminate atrial fibrillation. clinicaltrials.gov/show/NCT01873352 (first received 2013).

NCT01888315 {published data only}

NCT01888315. Influence of catheter-based renal denervation in diseases with increased sympathetic activity. clinicaltrials.gov/show/NCT01888315 (first received 2012).

NCT01897545 {published data only}

NCT01897545. The role of renal denervation in improving outcomes of catheter ablation in patients with atrial fibrillation and arterial hypertension. clinicaltrials.gov/show/NCT01897545 (first received 2012).

NCT01901549 {published data only}

NCT01901549. Renal denervation in patients after acute coronary syndrome. clinicaltrials.gov/show/NCT01901549 (first received 2013).

NCT01907828 {published data only}

NCT01907828. A feasibility study to evaluate the effect of concomitant renal denervation and cardiac ablation on AF recurrence. clinicaltrials.gov/show/NCT01907828 (first received 2013).

NCT01932450 {published data only}

NCT01932450. Radiofrequency ablation for ADPKD blood pressure and disease progression control. clinicaltrials.gov/show/NCT01932450 (first received 2013).

NCT02016573 {published data only}

NCT02016573. Renal denervation for uncontrolled hypertension. clinicaltrials.gov/show/NCT02016573 (first received 2013).

NCT02057224 {published data only}

NCT02057224. Metabolic and cardiovascular effects of renal denervation. clinicaltrials.gov/show/NCT02057224 (first received 2014).

NCT02115100 {published data only}

NCT02115100. Treatment of atrial fibrillation in patients by pulmonary vein isolation, renal artery denervation or both. clinicaltrials.gov/show/NCT02115100 (first received 2014).

NCT02115230 {published data only}

NCT02115230. Transcatheter renal denervation in heart failure with normal left ventricular ejection fraction - a safety and efficacy study of irrigated radiofrequency catheter. clinicaltrials.gov/show/NCT02115230 (first received 2014).

NCT02155790 {published data only}

NCT02155790. The Peregrine study: a safety and performance study of renal denervation. clinicaltrials.gov/show/NCT02155790 (first received 2014).

NCT02164435 {published data only}

NCT02164435. Effects of renal sympathetic denervation on the cardiac and renal functions in patients with drug-resistant hypertension through MRI evaluation (RDN). clinicaltrials.gov/show/NCT02164435 (first received 2014).

NCT02272920 {published data only}

NCT02272920. PCI and renal denervation in hypertensive patients with acute coronary syndromes. clinicaltrials.gov/show/NCT02272920 (first received 2014).

NCT02559882 {published data only}

NCT02559882. Testing effectiveness of renal denervation in patients with therapy-resistant hypertension. clinicaltrials.gov/show/NCT02559882 (first received 2015).

NCT02667912 {published data only}

Baev, APekarskiy, SMordovin, VRipp, TFalkovskaya, ALichikaki, V et al. A distal mode of renal denervation in segmental branches of renal artery versus conventional main trunk therapy: a double blind randomized controlled study in patients with resistant hypertension. Journal of the american college of cardiology 2017;18 Suppl 1:B86. [Google Scholar]
NCT02667912. Distal renal denervation. clinicaltrials.gov/show/NCT02667912 (first received 2016).
Pekarskiy, SBaev, AMordovin, VSemke, GRipp, TFalkovskaya, A et al. Distal renal denervation performed mainly in segmental branches of renal artery versus conventional mode of the intervention: A randomized controlled trial in patients with resistant hypertension. European Heart Journal 2016;37 Suppl 1:78. [Google Scholar]

NCT03261375 {published data only}

NCT03261375. A clinical trial to evaluate safety and efficacy of a renal denervation system in treatment of hypertension. ClinicalTrials.gov/show/NCT03261375 2017.

NCT03465917 {published data only}

NCT03465917. Physiological study of the efficacy and mechanistic effects of alcohol renal denervation. ClinicalTrials.gov/show/NCT03465917 2018.

NCT03511313 {published data only}

NCT03511313. Renal denervation with sterile irrigated deflectable ablation catheter used in renal artery in primary hypertension. ClinicalTrials.gov/show/NCT03511313 2018.

NCT04248530 {published data only}

DENEX renal denervation in patients With uncontrolled hypertension: safety study. clinicaltrials.gov/show/NCT04248530.

NCT04264403 {published data only}

Renal denervation in chronic kidney disease - RDN-CKD study. https://clinicaltrials.gov/show/NCT04264403 (first received 11 February 2020).

NCT04307836 {published data only}

DENEX renal denervation in patients with hypertension on no or 1-3 antihypertensive medications (DENEX HTN-KORAS). clinicaltrials.gov/show/NCT04307836 (first received 13 March 2020).

NCT04311086 {published data only}

SPYRAL DYSTAL clinical study. clinicaltrials.gov/show/NCT04311086 (first received 17 March 2020).

NCT04535050 {published data only}

DENEX renal denervation in patients with hypertension on no antihypertensive medications. clinicaltrials.gov/show/NCT04535050 (first received 1 September 2020).

Palionis 2016 {published data only}

Palionis D, Berukstis A, Misonis N, Ryliskyte L, Celutkiene J, Zakarkaite D, et al . Could careful patient selection for renal denervation warrant a positive effect on arterial stiffness and left ventricular mass reduction? Acta cardiologica 2016;71:173-83. [DOI] [PubMed] [Google Scholar]

Pekarskiy 2016 {published data only}

Pekarskiy S, Baev A, Mordovin V, Semke G, Ripp T, Falkovskaya A, et al. Distal renal denervation performed mainly in segmental branches of renal artery versus conventional mode of the intervention: A randomized controlled trial in patients with resistant hypertension. European Heart Journal 2016;37 Suppl 1:78. [Google Scholar]

Pekarskiy 2020 {published data only}

Pekarskiy S. TCT CONNECT-416 powerful antihypertensive effect of anatomically optimized distal renal denervation 3 years after the procedure according to a double-blind randomized controlled study. Journal of the American College of Cardiology 2020;76(17 Suppl ):B178-9. [DOI: 10.1016/j.jacc.2020.09.441] [DOI] [Google Scholar]

Persu 2018 {published data only}

Persu A, Renkin J, Hochul M, Wojakowski W, Bohm M, Mahfoud F, et al. Chemical renal denervation with alcohol - Long term results from the peregrine post-market study. Journal of Hypertension 2018;36 Suppl 1:e123. [Google Scholar]

Petrov 2019 {published data only}

Petrov I, Tasheva I, Garvanski I, Tankov Z, Simova I. Comparison of standard renal denervation procedure versus novel distal and branch vessel procedure with brachial arterial access. Cardiovascular Revascularization Medicine 2019;20(1):38-42. [DOI] [PubMed] [Google Scholar]

Pokushalov 2012 {published data only}

Pokushalov E, Romanov A, Artyomenko S, Turov A, Shirokova N, Karaskov A. Renal denervation and pulmonary vein isolation in patients with drug resistant hypertension and symptomatic atrial fibrillation. European Heart Journal 2012;33:382. [DOI] [PubMed] [Google Scholar]

Pokushalov 2012a {published data only}

Pokushalov E, Romanov A, Artyomenko S, Turov A, Shirokova N, Karaskov A. Renal denervation and pulmonary vein isolation in patients with drug resistant hypertension and symptomatic atrial fibrillation. Heart Rhythm 2012;1:S172. [Google Scholar]

Pokushalov 2012b {published data only}

Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, et al. A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. Journal of the American College of Cardiology 2012;60:1163-70. [DOI] [PubMed] [Google Scholar]

Pokushalov 2014 {published data only}

Pokushalov E, Romanov A, Katritsis D, Artyomenko S, Bayramova S, Losik D, et al. The role of renal denervation in improving outcomes of catheter ablation in patients with atrial fibrillation and moderate resistant or resistant hypertension. Journal of the American College of Cardiology 2014;1:A280. [DOI] [PubMed] [Google Scholar]

Pokushalov 2014a {published data only}

Pokushalov E, Romanov A, Katritsis D, Artyomenko S, Bayramova S, Losik D, et al. Renal denervation for improving outcomes of catheter ablation in patients with atrial fibrillation and hypertension: early experience. European Heart Journal 2014;35:434-5. [DOI] [PubMed] [Google Scholar]

Pokushalov 2014b {published data only}

Pokushalov E, Romanov A, Katritsis DG, Artyomenko S, Bayramova S, Losik D, et al. Renal denervation for improving outcomes of catheter ablation in patients with atrial fibrillation and hypertension: early experience. Heart Rhythm 2014;11:1131-8. [DOI] [PubMed] [Google Scholar]

RADIANCE‐HTN SOLO {published data only}

Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, et al. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet 2018;391:2335-45. [DOI] [PubMed] [Google Scholar]

RADIANCE II {published data only}

NCT03614260. The RADIANCE II pivotal study: a study of the recor medical paradise system in stage II hypertension. ClinicalTrials.gov/show/NCT03614260 (first received 3 August 2018);(first received 10 August 2005).

RAPID {published data only}

NCT01520506. Rapid renal sympathetic denervation for resistant hypertension (RAPID). clinicaltrials.gov/show/NCT01520506 (first received 2012).

ReD {published data only}

NCT01355055. Sympathetic activity and renal denervation (ReD). clinicaltrials.gov/show/NCT01355055 (first received 2011).

REDUCE HTN:REINFORCE {published data only}

NCT02392351. Renal denervation using the Vessix Renal Denervation system for the treatment of hypertension (REDUCE HTN:REINFORCE). clinicaltrials.gov/show/NCT02392351 (first received 2015).

Ripp 2019 {published data only}

Ripp T, Ryabova T, Pekarskiy S, Mordovin V, Buharova E, Anfinogenova YA, et al. Cardiac function, structure, and speckle-tracking echocardiography-derived parameters after distal and conventional renal denervation: a double-blind randomized study. European heart journal 2019;40:665. [DOI: 10.1093/eurheartj/ehz748.0031] [DOI] [Google Scholar]

RNS‐NTR 4384 {published data only}

NTR4384. Feasibility of electrical mapping and stimulation of renal arteries in patients undergoing renal denervation. https://trialregister.nl/trial/4239 2014.

RSDAH {published data only}

NCT02642445. Renal sympathetic denervation from the adventitia on hypertension (RSDAH). clinicaltrials.gov/show/NCT02642445 (first received 2015).

Sanders 2016 {published data only}

Sanders M, De Jager R, Bots M, Lobo M, Blankestijn P. Renal denervation in hypertensive patients not on blood pressure lowering drugs. Journal of Hypertension 2016;34 Suppl 2:e94-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

Saxena 2017 {published data only}

Saxena M, Lobo MD, O'Brien BO, Toennes C, Gertner SW, Dawood M, et al. Phase II randomized sham-controlled study of renal denervation for subjects with uncontrolled hypertension-WAVE IV. Journal of Human Hypertension 2017;31 (10):679. [Google Scholar]

Saxena 2018 {published data only}

Saxena M, Shour T, Shah M, Wolff CB, Julu POO, Kapil V, et al. Attenuation of splanchnic autotransfusion following noninvasive ultrasound renal denervation: a novel marker of procedural success. Journal of the American Heart Association 2018;7(12):12. [DOI] [PMC free article] [PubMed] [Google Scholar]

Scalise 2020 {published data only}

Scalise F, Sole A, Singh G, Sorropago A, Sorropago G, Ballabeni C, et al. Renal denervation in patients with end-stage renal disease and resistant hypertension on long-term haemodialysis. Journal of Hypertension 2020;38(5):936-42. [DOI] [PubMed] [Google Scholar]

Schmieder 2017 {published data only}

Schmieder RE, Ott C, Toennes S, Gertner M, Dawood O, Saxena M, et al. Phase II randomized sham-controlled study of renal denervation for subjects with uncontrolled hypertension-wave IV. Journal of Hypertension 2017;35 Suppl 2:e21. [DOI] [PubMed] [Google Scholar]

Schmieder 2018 {published data only}

Schmieder RE, Ott C, Toennes SW, Bramlage P, Gertner M, Dawood O, et al. Phase II randomized sham-controlled study of renal denervation for individuals with uncontrolled hypertension - WAVE IV. Journal of Hypertension 2018;36(3):680-9. [DOI] [PubMed] [Google Scholar]

Shipman 2014 {published data only}

Shipman KE. A controlled trial of renal denervation for resistant hypertension. Annals of Clinical Biochemistry 2014;51:621. [Google Scholar]

Shugushev 2019 {published data only}

Shugushev Z, Maximkin DA, Chepurnoy A, Safonova O, Faibushevich A. Sympathetic renal denervation in patients with refractory arterial hypertension: 2-years follow-up. European Heart Journal 2019;21(Suppl 1):562. [DOI: 10.1093/eurheartj/ehz745.0954] [DOI] [Google Scholar]

Shugushev 2019b {published data only}

Shugushev Z, Maximkin D, Alexandr C, Faibushevich A, Safonova O, Mambetov A. TCT-605 sympathetic renal denervation in patients with refractory arterial hypertension: 2-year follow-up. Journal of the American College of Cardiology 2019;74(13 Suppl ):B594. [DOI: 10.1016/j.jacc.2019.08.718] [DOI] [Google Scholar]

Sievert 2014 {published data only}

Sievert H, Kipshidze NN, Kipiani K, Kipiani V, Mukhuradze T, Wholey M. First clinical experience with neurotropic agents for treatment of sympathetic hypertension. Journal of the American College of Cardiology 2014;1(11):B119. [PubMed] [Google Scholar]

Sitkova 2020 {published data only}

Sitkova ES, Mordovin VF, Pekarsky SE, Ripp TM, Falkovskaya AYu, Lichikaki VA, et al. Distal renal denervation: cardioprotection in patients with resistant hypertension. Cardiovascular therapy and prevention (russian federation) 2020;19:no pagination. [DOI: 10.15829/1728-8800-2019-2225] [DOI] [Google Scholar]

SPYRAL HTN‐OFF MED {published data only}

NCT02439749. Global clinical study of renal denervation with the SYMPLICITY SPYRAL™ multi-electrode renal denervation system in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED). clinicaltrials.gov/show/NCT02439749 (first received 12 May 2015).

SPYRAL HTN‐ON MED {published data only}

NCT02439775. Global clinical study of renal denervation with the SYMPLICITY SPYRAL™ multi-electrode renal denervation system in patients with uncontrolled hypertension on standard medical therapy (SPYRAL HTN-ON MED). clinicaltrials.gov/show/NCT02439775 (first received 12 May 2015).

Stoiber 2018 {published data only}

Stoiber L, Mahfoud F, Zamani SM, Lapinskas T, Bohm M, Ewen S, et al. Renal sympathetic denervation restores aortic distensibility in patients with resistant hypertension: data from a multi-center trial. Clinical Research in Cardiology 2018;107(8):642-52. [DOI] [PMC free article] [PubMed] [Google Scholar]

SYMPLICITY 2011 {published data only}

SYMPLICITY HTN Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension 2011;57:911-7. [DOI] [PubMed] [Google Scholar]

SYMPLICITY AF {published data only}

NCT02064764. Renal nerve denervation in patients with hypertension and paroxysmal and persistent atrial fibrillation (SYMPLICITY AF). clinicaltrials.gov/show/NCT02064764 (first received 17 February 2014).

TARGET BP OFF‐MED {published data only}

NCT03503773. The TARGET BP OFF-MED trial. ClinicalTrials.gov/show/NCT03503773 (first received 20 April 2018).

Townsend 2017 {published data only}

Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet 2017;390:2160-70. [DOI] [PubMed] [Google Scholar]

Tsioufis 2016 {published data only}

Tsioufis C, Dimitriadis K, Kasiakogias A, Kalos T, Liatakis I, Koutra E, et al . Effects of multielectrode renal denervation on sympathetic nerve activity and insulin resistance in metabolic syndrome. Journal of Hypertension 2016;34 Suppl 2:e78. [DOI] [PubMed] [Google Scholar]

UMIN000012020 {published data only}

UMIN000012020. Study of renal sympathetic denervation with radiofrequency ablation catheter for resistant essential hypertension. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014034 2013.

Wage 2015 {published data only}

Wage R, Patel H, Smith GC, Keegan J, Gatehouse P, Vassiliou V, et al. The utility of magnetic resonance imaging in a trial to assess the effect of renal denervation in heart failure with preserved ejection fraction. Journal of Cardiovascular Magnetic Resonance 2015;17(S1):T7. [Google Scholar]

Waksman 2016 {published data only}

Waksman R, Bakris GL, Steinvil A, Garcia-Garcia HM, Debruin V, Jolivette D, et al. SYMPLICITY HTN-3 screen failure patient cohort analysis. European Heart Journal 2016;37 Suppl 1:230. [Google Scholar]

WAVE IV {published data only}

NCT02029885. Sham controlled study of renal denervation for subjects with uncontrolled hypertension (WAVE IV). clinicaltrials.gov/show/NCT02029885 (first received 8 January 2014).

Wave VI {published data only}

NCT02480517. Wave VI feasibility study: Phase II randomized sham controlled study of renal denervation for untreated Stage I and II hypertension. clinicaltrials.gov/show/NCT02480517 (first received 24 June 2015).

Weber 2018 {published data only}

Weber MA, Kandzari D, Bohm M, Mahfoud F, Kario K, Walton T, et al. Adherence to antihypertensive drugs: Insights from the spyral HTN trials and implications for hypertension trial design. Hypertension 2018;72 Suppl 1:no pagination. [Google Scholar]

Weber 2020 {published data only}

Weber MA, Kirtane AJ, Weir MR, Radhakrishnan JD, Berk T, Mendelsohn M, et al. The REDUCE HTN: REINFORCE: randomized, sham-controlled trial of bipolar radiofrequency renal denervation for the treatment of hypertension. JACC. Cardiovascular interventions 2020;13(4):461-70. [DOI: 10.1016/j.jcin.2019.10.061] [DOI] [PubMed] [Google Scholar]

Witkowski 2011 {published data only}

Witkowski A, Prejbisz A, Florczak E, Kadziela J, Sliwinski P, Bielen P, et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension 2011;58:559-65. [DOI] [PubMed] [Google Scholar]

Xiang 2014 {published data only}

Xiang C, Xu YL, Liu ZJ, Yan PY, Gao JQ, Gao BL. Effects of catheter-based renal sympathetic denervation at different segments of the renal artery on resistant hypertension. Experimental and Clinical Cardiology 2014;20:145-56. [Google Scholar]
Xu YL, Liu ZJ, Jin HG, Gao JQ, Yan PY, Zhang WQ, et al. Effect of ablation sites in catheter-based renal sympathetic denervation on anti-hypertension results in patients with resistant hypertension. Academic Journal of Second Military Medical University 2014;35:191-4. [Google Scholar]

Yin 2013 {published data only}

Yin Y, Chen W, Ling Z, Xu Y, Liu Z, Su L, et al. Preliminary effects of renal sympathetic denervation with saline irrigated catheter on systolic function in patients with heart failure - a feasibility report from the swan-HF pilot study. Circulation 2013;128(S22):A17684. [Google Scholar]

Zhang 2014 {published data only}

Zhang ZH, Yang K, Jiang FL, Zeng LX, Jiang WH, Wang XY. The effects of catheter-based radiofrequency renal denervation on renal function and renal artery structure in patients with resistant hypertension. Journal of Clinical Hypertension 2014;16:599-605. [DOI] [PMC free article] [PubMed] [Google Scholar]

References to ongoing studies

ALLEGRO‐HTN {published data only}

NCT01874470. Renal denervation by Allegro system in patients with resistant hypertension. clinicaltrials.gov/show/NCT01874470 (first received 2013).

DEPART {published data only}

NCT01522430. Denervation of renal sympathetic activity and hypertension study. clinicaltrials.gov/show/NCT01522430 (first received 2012).

EnligHTN IV {published data only}

NCT01903187. Multi-center, randomized, single-blind, sham controlled clinical investigation of renal denervation for uncontrolled hypertension. clinicaltrials.gov/show/NCT01903187 (first received 2013).

ENSURE {published data only}

NCT02102126. Effect of renal denervation on arterial stiffness and haemodynamics in patients with uncontrolled hypertension (ENSURE). clinicaltrials.gov/show/NCT02102126 (first received 2014).

KPS {published data only}

NCT02002585. Renal protection using sympathetic denervation in patients with chronic kidney disease (Kidney protection study - KPS Study). clinicaltrials.gov/show/NCT02002585 (first received 2013).

NCT01848275 {published data only}

NCT01848275. Full length versus proximal renal arteries ablation. clinicaltrials.gov/show/NCT01848275 (first received 2011).

NCT01918111 {published data only}

NCT01918111. Effects of renal denervation for resistant hypertension on exercise diastolic function and regression of atherosclerosis and the evaluation of new methods predicting a successful renal sympathetic denervation (RENEWAL-EXERCISE, -REGRESS, and -PREDICT trial from RENEWAL RDN Registry). clinicaltrials.gov/show/NCT01918111 (first received 2013).

NCT01968785 {published data only}

NCT01968785. Renal denervation in patients with uncontrolled blood pressure. clinicaltrials.gov/show/NCT01968785 (first received 2013).

NCT02021019 {published data only}

NCT02021019. Renal denervation to improve outcomes in patients with end-stage renal disease. clinicaltrials.gov/show/NCT02021019 (first received 2014).

NCT02346045 {published data only}

NCT02346045. Effect of renal denervation in end stage renal disease with resistant hypertension. clinicaltrials.gov/show/NCT02346045 (first received 2014).

NCT02444442 {published data only}

NCT02444442. The Australian SHAM controlled clinical trial of renal denervation in patients with resistant hypertension (AUSHAM RDN-01). clinicaltrials.gov/show/NCT02444442 (first received 2015).

NCT02608632 {published data only}

NCT02608632. High frequency guided renal artery denervation for improving outcome of renal ablation procedure. clinicaltrials.gov/show/NCT02608632 (first received 2015).

NCT02900729 {published data only}

Liu Z, Shen L, Huang W, Zhao X, Fang W, Wang C, et al. Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial. BMJ Open 2017;7(9):e015672. [DOI] [PMC free article] [PubMed] [Google Scholar]

NTR3444 {published data only}

NTR3444. Endovascular renal sympathetic denervation versus spironolactone in treatment-resistant hypertension: a randomized, multicentric study (RRSS trial). www.trialregister.nl/trialreg/admin/rctview.asp?TC=3444 (first received 2012).

PaCE {published data only}

NCT01895140. A study of renal denervation in patients with treatment resistant hypertension. clinicaltrials.gov/ct2/show/NCT01895140 (first received 2013).

RADIANCE‐HTN {published data only}

Azizi M, Basile J, Daemen J, Davies J, Francis D, Kirtane A, et al. The "rADIANCE-HTN" clinical study: a two-cohort study design to evaluate the effectiveness of the paradise renal denervation system in patients with hypertension. Journal of the American Society of Hypertension 2016;10(4 Suppl):e39. [Google Scholar]
NCT02649426. A study of the ReCor Medical Paradise system in clinical hypertension (RADIANCE-HTN). clinicaltrials.gov/show/NCT02649426 (first received 2016).

RAPID II {published data only}

NCT01939392. Rapid renal sympathetic denervation for resistant hypertension using the OneShot renal denervation system II (RAPID II). clinicaltrials.gov/show/NCT01939392 (first received 2013).

RDNP‐2012‐01 {published data only}

NCT01865240. Renal denervation for resistant hypertension. clinicaltrials.gov/show/NCT01865240 (first received 2013).

RENO {published data only}

NCT01617551. Effect of renal denervation on no-mediated regulation of salt and water excretion, vasoactive hormones and tubular transport proteins in patients with resistant hypertension (RENO). clinicaltrials.gov/show/NCT01617551 (first received 2012).

RENSYMPIS {published data only}

NCT01785732. Renal sympathetic denervation and insulin sensitivity (RENSYMPIS study). clinicaltrials.gov/show/NCT01785732 (first received 2013).

ReSET‐2 {published data only}

NCT01762488. Renal denervation in treatment resistant hypertension, a double-blind randomized controlled trial (ReSET-2). clinicaltrials.gov/show/NCT01762488 (first received 2013).

RSD4CKD {published data only}

NCT01737138. Safety and effectiveness study of percutaneous catheter-based renal sympathetic denervation in patients with chronic kidney disease and resistant hypertension. clinicaltrials.gov/show/NCT01737138 (first received 2012).

RSDARH {published data only}

NCT03758196. Renal sympathetic denervation from the adventitia on resistant hypertension (RSDARH）. clinicaltrials.gov/show/NCT03758196 (first received 29 November 2018 ).

RSDforAF {published data only}

NCT01713270. Safety and effectiveness study of percutaneous catheter-based renal sympathetic denervation in patients with drug-resistant hypertension and symptomatic atrial fibrillation. clinicaltrials.gov/show/NCT01713270 (first received 2012).
Qiu M, Yin Y, Shan Q. Renal sympathetic denervation versus antiarrhythmic drugs for drug-resistant hypertension and symptomatic atrial fibrillation (RSDforAF) trial: study protocol for a randomized controlled trial. Trials 2013;14:168. [DOI] [PMC free article] [PubMed] [Google Scholar]

SYMPLICITY HTN‐4 {published data only}

NCT01972139. Renal denervation in patients with uncontrolled hypertension - SYMPLICITY HTN-4. clinicaltrials.gov/show/NCT01972139 (first received 2013).

Additional references

Agasthi 2019

Agasthi P, Shipman J, Arsanjani R, Ashukem M, Girardo ME, Yerasi C, et al. Renal denervation for resistant hypertension in the contemporary era: a systematic review and meta-analysis. Scientific Reports 2019;9(1):6200. [DOI] [PMC free article] [PubMed] [Google Scholar]

Calhoun 2008

Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation 2008;117(25):e510-26. [DOI] [PubMed] [Google Scholar]

Davis 2013

Davis MI, Filion KB, Zhang D, Eisenberg MJ, Afilalo J, Schiffrin EL, et al. Effectiveness of renal denervation therapy for resistant hypertension: a systematic review and meta-analysis. Journal of the American College of Cardiology 2013;16(3):231-41. [DOI] [PubMed] [Google Scholar]

Esler 2015

Esler M. Renal denervation: not as easy as it looks. Science Translational Medicine 2015;7(285):285fs18. [DOI] [PubMed] [Google Scholar]

Fadl Elmula 2017

Fadl Elmula M, Feng Y-M, Jacobs L, Larstorp AC, Kjeldsen SE, Pers A, European Network COordinating research on Renal Denervation (ENCOReD). Sham or no sham control: that is the question in trials of renal denervation for resistant hypertension. A systematic meta-analysis. Blood Pressure 2017;26(4):195-203. [DOI] [PubMed] [Google Scholar]

GRADEpro GDT 2015 [Computer program]

GRADEpro Guideline Development Tool. Version (accessed prior to 25 October 2021). Hamilton (ON): McMaster University (developed by Evidence Prime, Inc.), 2015. www.guidelinedevelopment.org.

Guyatt 2008

Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924-6. [DOI] [PMC free article] [PubMed] [Google Scholar]

Higgins 2003

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557-60. [DOI] [PMC free article] [PubMed] [Google Scholar]

Higgins 2011

Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1.

Huan 2013

Huan Y, Cohen DL. Renal denervation: a potential new treatment for severe hypertension. Clinical Cardiology 2013;36(1):10-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

Judd 2014

Judd E, Calhoun DA. Apparent and true resistant hypertension: definition, prevalence and outcomes. Journal of Human Hypertension 2014;28(8):463-8. [DOI: 10.1038/jhh.2013.140] [DOI] [PMC free article] [PubMed] [Google Scholar]

Kandzari 2015

Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M, et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. European Heart Journal 2015;36(4):219-27. [DOI] [PMC free article] [PubMed] [Google Scholar]

Leong 2014

Leong KT, Walton A, Krum H. Renal sympathetic denervation for the treatment of refractory hypertension. Annual Review of Medicine 2014;65:349-65. [DOI] [PubMed] [Google Scholar]

Myat 2012

Myat A, Redwood SR, Qureshi AC, Spertus JA, Williams B. Resistant hypertension. BMJ 2012;345:e7473. [DOI] [PubMed] [Google Scholar]

Nakagawa 2013a

Nakagawa T, Hasegawa Y, Uekawa K, Ma M, Katayama T, Sueta D, et al. Renal denervation prevents stroke and brain injury via attenuation of oxidative stress in hypertensive rats. Journal of the American Heart Association 2013;2(5):e000375. [DOI] [PMC free article] [PubMed] [Google Scholar]

Nakagawa 2013b

Katayama T, Sueta D, Kataoka K, Hasegawa Y, Koibuchi N, Toyama K, et al. Long-term renal denervation normalizes disrupted blood pressure circadian rhythm and ameliorates cardiovascular injury in a rat model of metabolic syndrome. Journal of the American Heart Association 2013;2(4):e000197. [DOI] [PMC free article] [PubMed] [Google Scholar]

RevMan 2014 [Computer program]

Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Sakakura 2014

Sakakura K, Ladich E, Cheng Q, Otsuka F, Yahagi K, Fowler DR, et al. Anatomic assessment of sympathetic peri-arterial renal nerves in man. Journal of the American College of Cardiology 2014;64(7):635-43. [DOI] [PubMed] [Google Scholar]

References to other published versions of this review

Coppolino 2017

Giuseppe Coppolino, Anna Pisano, Laura Rivoli, Davide Bolignano. Renal denervation for resistant hypertension.. Review Cochrane Database Syst Rev. 2017;21(2):CD011499. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0001] Azizi M, Sapoval M, Gosse P, Monge M, Bobrie G, Delsart P, et al. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENER-HTN): a multicentre, open-label, randomised controlled trial. Lancet 2015;385(9981):1957-65. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0002] Forni O, Pereira V, Sapoval E, Azizi M. Prevalence and risk factors for refractory hypertension in the DENER-HTN study. Journal of Hypertension 2015;33:e51. [Google Scholar]

[CD011499-bib-0003] NCT01570777. Renal denervation in hypertension [Renal denervation in patients with resistant hypertension ]. clinicaltrials.gov/show/NCT01570777 (first received 2 April 2012).

[CD011499-bib-0004] Sapoval MR, Monge M, Pereira H, Azizi M. DENER-HTN trial: a prospective randomized control trial of the efficacy of renal artery denervation in resistant hypertension. Cardiovascular and Interventional Radiology 2014;1:S341. [Google Scholar]

[CD011499-bib-0005] De La Sierra A, Pareja J, Armario P, Barrera A, Sans L, Vazquez S, et al. Renal denervation versus spironolactone in resistant hypertension. effects on circadian patterns and blood pressure variability. Journal of Hypertension 2016;34(Suppl 2):e43. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0006] De la Sierra A, Pareja J, Armario P, Barrera A, Yun S, Vazquez S, et al. Renal denervation vs. spironolactone in resistant hypertension: effects on circadian patterns and blood pressure variability. American Journal of Hypertension 2017;30:37-41. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0007] NCT02039492. Sympathetic renal denervation versus increment of pharmacological treatment in resistant arterial hypertension [Sympathetic renal denervation versus increment of pharmacological treatment in resistant arterial hypertension]. clinicaltrials.gov/show/NCT02039492 (first received 2012).

[CD011499-bib-0008] Oliveras A, Armario P, Clara A, Sans-Atxer L, Vazquez S, Pascual J, et al. Spironolactone versus sympathetic renal denervation to treat true resistant hypertension: results from the DENERVHTA study: a randomized controlled trial. Journal of Hypertension 2016;34:1863–71. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0009] Oliveras A, Armario P, Sans L, Clara A, Vazquez S, Molina L, et al. Organ damage changes in patients with resistant hypertension randomized to renal denervation or spironolactone: the DENERVHTA (Denervacion en Hipertension Arterial) study. Journal of Clinical Hypertension 2018;20(1):69-75. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0010] Oliveras A, Armario P, Sans L, Clara A, Vazquez S, Molina L, et al. Preclinical target organ damage changes in patients with resistant hypertension randomized to renal denervation or spironolactone as add-on therapy. results from the DENERVHTA study. Hypertension 2016;68(Suppl 1):10. [Google Scholar]

[CD011499-bib-0011] Oliveras A, Armario P, Sans L, Clara A, Vazquez S, Molina LL, et al. Changes in subclinical organ damage in patients with resistant hypertension randomized to receive renal denervation or spironolactone as add-on therapy.the Denervhta study results. Journal of Hypertension 2016;34(Suppl 2):e47. [Google Scholar]

[CD011499-bib-0012] Desch S, Okon T, Heinemann D, Kulle K, Rohnert K, Sonnabend M, et al. Randomized sham-controlled trial of renal sympathetic denervation in mild resistant hypertension. Hypertension 2015;65:1202-8. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0013] Fengler K, Heinemann D, Okon T, Röhnert K, Stiermaier T, Von Röder M, et al. Renal denervation improves exercise blood pressure: insights from a randomized, sham-controlled trial. Clinical Research in Cardiology 2016;105(7):592–600. [DOI: 10.1007/s00392-015-0955-8] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0014] NCT01656096. Renal sympathetic denervation in mild refractory hypertension [Renal sympathetic denervation in patients with mild refractory hypertension]. clinicaltrials.gov/show/NCT01656096 (first received 31 July 2012).

[CD011499-bib-0015] Franzen KF, Mortensen K, Himmel F, Stritzke J, Koester J, Bock J, et al. Percutaneous renal denervation (PRD) improves central hemodynamics and arterial stiffness - a pilot study. European Heart Journal 2012;33:771. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0016] Kario K, Bakris G, Bhatt LD. Preferential reduction in morning/nocturnal hypertension by renal denervation for drug-resistant hypertension: a new ABPM analysis of SYMPLICITY HTN-3 and HTN-Japan. Journal of Hypertension 2015;33(Suppl 1):e52. [DOI: 10.1097/01.hjh.0000467484.20438.39] [DOI] [Google Scholar]

[CD011499-bib-0017] Kario K, Bhatt DL, Brar S, Cohen SA, Fahy M, Bakris GL. Effect of catheter-based renal denervation on morning and nocturnal blood pressure: insights from SYMPLICITY HTN-3 and SYMPLICITY HTN-Japan. Hypertension 2015;66:1130-7. [EMBASE: 10.1161/HYPERTENSIONAHA.115.06260] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0018] Kario K, Ogawa H, Okumura K, Okura T, Saito S, Ueno T, et al. SYMPLICITY HTN-Japan - First randomized controlled trial of catheter-based renal denervation in Asian patients. Circulation Journal 2015;79:1222-9. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0019] NCT01644604. Renal denervation by MDT-2211 system in patients with uncontrolled hypertension [The clinical study of renal denervation by MDT-2211 system in patients with uncontrolled hypertension]. clinicaltrials.gov/show/NCT01644604 (first received 29 June 2012).

[CD011499-bib-0020] Jacobs L, Persu A, Huang QF, Lengele JP, Thijs L, Hammer F, et al. Results of a randomized controlled pilot trial of intravascular renal denervation for management of treatment-resistant hypertension. Blood Pressure 2017;26(6):321-31. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0021] Jin Y, Jacobs L, Baelen M, Thijs L, Renkin J, Hammer F, et al. Rationale and design of the investigator-steered project on intravascular renal denervation for management of drug-resistant hypertension (INSPiRED) trial. Blood Pressure 2014;23:138-46. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0022] Jin Y, Jocobs L, Hammer F, Renkin J, Persu A, Staessen JA. Rationale and design of the investigator-steered project on intravascular renal denervation for management of drug-resistant hypertension (INSPiRED) trial. Journal of the American Society of Hypertension 2014;8(S4):e71. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0023] NCT01505010. Renal denervation for management of drug-resistant hypertension [Investigator-steered project on intravascular renal denervation for management of drug-resistant hypertension ]. clinicaltrials.gov/show/NCT01505010 (first received 2012). [DOI] [PMC free article] [PubMed]

[CD011499-bib-0024] Moiseeva A, Caraus A, Moscalu V, Calenici O, Ciobanu N, Sapojnic N, et al. The influence of renal denervation treatment on blood pressure in patients with resistant hypertension. European Journal of Preventive Cardiology 2020;26:P711. [Google Scholar]

[CD011499-bib-0025] Moiseeva A, Caraus A, Ciobanu N, Moscalu V, Surev A, Abras M, et al. The effects of renal artery denervation on blood pressure values and diastolic dysfunction in resistant hypertension. European Journal of Preventive Cardiology 2019;26(Suppl 1):S164-5. [Google Scholar]

[CD011499-bib-0026] Moiseeva A, Caraus A, Moscalu V, Calenici O, Ciobanu N, Sapojnic N, et al. The influence of renal denervation treatment on blood pressure in patients with resistant hypertension. European Journal of Preventive Cardiology 2020;27(1 Suppl 1):P711. [Google Scholar]

[CD011499-bib-0027] Moiseeva A, Caraus A, Ciobanu N Moscalu V, Surev A, Abras M, et al. The effects of renal artery denervation on blood pressure values and diastolic dysfunction in resistant hypertension. European Journal of Preventive Cardiology 2019;26(Suppl 1):S164-5. [Google Scholar]

[CD011499-bib-0028] Bergland OU , Søraas CL , Larstorp ACK, Halvorsen LV, Hjørnholm U, Hoffman P, et al. The randomised Oslo study of renal denervation vs. antihypertensive drug adjustments: efficacy and safety through 7 years of follow-up. Blood Pressure 2020;30:41-50. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0029] Bergo KK, Larstorp AC, Hoffmann P, Hjørnholm U, Cataliotti A, Høieggen A, et al. Renal sympathetic denervation lowers systemic vascular resistance in true treatment-resistant hypertension. Blood pressure 2020;30:31-40. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0030] Elmula MF, Hoffmann P, Larstorp AC, Brekke M, Fossum E, Stenehjem A, et al. Renal sympathetic denervation is inferior to adjusted drug treatment in patients with true treatment resistant hypertension, a randomized controlled trial. European Heart Journal 2014;35:718. [Google Scholar]

[CD011499-bib-0031] Elmula MF, Hoffmann P, Larstorp AC, Fossum E, Brekke M, Kjeldsen SE, et al. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension 2014;63:991-9. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0032] Elmula MF, Hoffmann P, Larstorp AC, Hoieggen A, Kjeldsen S. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment resistant hypertension, a randomized clinical trial. Journal of the American College of Cardiology 2014;1:A1306. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0033] Elmula MF, Larstorp AC, Hoffmann P, Rostrup M, Hoieggen A, Kjeldsen S. One-year outcomes of a randomized study in renal denervation: Results for Oslo-RDN study. European Heart Journal 2016;37(Suppl 1):1056-7. [Google Scholar]

[CD011499-bib-0034] Larstorp BK, Hoieggen ACK, Hjornholm A, Rostrup P, Elmula MF. Haemodynamic changes in patients with treatment-resistant hypertension after renal sympathetic denervation compared to individualized drug therapy. Journal of hypertension 2016;34(Suppl 2):e305. [Google Scholar]

[CD011499-bib-0035] NCT01673516. Effect of renal sympathetic denervation on resistant hypertension and cardiovascular hemodynamic in comparison to intensive medical therapy utilizing impedance cardiography [Effect of renal sympathetic denervation on resistant hypertension and cardiovascular hemodynamic in comparison to intensive medical therapy utilizing impedance cardiography]. clinicaltrials.gov/show/NCT01673516 (first received 17 August 2012).

[CD011499-bib-0036] Soeraas CL, Bergland O, Halvorsen LV, Larstorp AC, Hjornholm U, Kjaer VN, et al. Long-term outcome of the randomized Oslo-RDN study. Journal of hypertension 2018;36 Suppl 1:e238-9. [Google Scholar]

[CD011499-bib-0037] NCT01560312. Renal denervation in refractory hypertension [Renal denervation - hope for patients with refractory hypertension?]. clinicaltrials.gov/show/NCT01560312 (first received 16 May 2011).

[CD011499-bib-0038] Rosa J, Widimsky P, Tousek P, Petrak O, Curila K, Waldauf P, et al. Randomized comparison of renal denervation versus intensified pharmacotherapy including spironolactone in true-resistant hypertension: six-month results from the Prague-15 study. Hypertension 2015;65:407-13. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0039] Rosa J, Widimsky P, Waldauf P, Lambert L, Zelinka T, Taborsky M, et al. Role of adding spironolactone and renal denervation in true resistant hypertension: one-year outcomes of randomized PRAGUE-15 study. Hypertension 2016;67:397-403. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0040] Rosa J, Widimsky P, Waldauf P, Lambert L, Zelinka T, Taborsky M, et al. The role of adding spironolactone and renal denervation in true resistant hypertension. One-year outcomes of randomized study. European Heart Journal 2016;37 Suppl 1:230. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0041] Rosa J, Widimsky P, Waldauf P, Zelinka T, Petrak O, Taborsky M, et al. Renal denervation in comparison to intensified pharmacotherapy in true resistant hypertension. Two-year outcomes of randomised PRAGUE-15 study. European Heart Journal 2017;38 Suppl 1:157. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0042] Rosa J, Widmsky P, Waldauf P, Zelinka T, Petak O, Taborsky M, et al. Renal denervation in comparison with intensified pharmacotherapy in true resistant hypertension: 2-year outcomes of randomized PRAGUE-15 study. Journal of Hypertension 2017;35:1093–9. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0043] Rosa J, Zelinka T, Petrak O, Strauch B, Somloova Z, Indra T, et al. Importance of thorough investigation of resistant hypertension before renal denervation: should compliance to treatment be evaluated systematically? Journal of Human Hypertension 2014;28:684-8. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0044] Tousek P, Widimsky J, Rosa J, Curila K, Branny M, Nykl I, et al. Catheter-based renal denervation versus intensified medical treatment in patients with resistant hypertension: rationale and design of a multicenter randomized study - PRAGUE-15. Cor et Vasa 2014;56:e235-9. [Google Scholar]

[CD011499-bib-0045] Ahmed H, Neuzil P, Schejbalova M, Bejr M, Kralovec S, Reddy VY. Renal sympathetic denervation for the management of chronic hypertension (RELIEF): 40 patient analysis. Circulation 2012;1(126):A17520. [Google Scholar]

[CD011499-bib-0046] Ahmed H, Neuzil P, Schejbalova M, Bejr M, Kralovec S, Reddy VY. Renal sympathetic denervation for the management of chronic hypertension (RELIEF): an interim analysis. Heart Rhythm 2012;1:S469-70. [Google Scholar]

[CD011499-bib-0047] NCT01628172. Renal sympathetic denervation for the management of chronic hypertension [Renal sympathetic denervation for the management of chronic hypertension]. clinicaltrials.gov/show/NCT01628172 (first received 2012).

[CD011499-bib-0048] Engholm M, Bertelsen JB, Mathiassen ON, Botker HE, Vase H, Peters CD, et al . Effects of renal denervation on coronary flow reserve and forearm dilation capacity in patients with treatment-resistant hypertension. A randomized, double-blinded, sham-controlled clinical trial. International Journal of Cardiology 2018;250:29-34. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0049] Mathiassen O, Bech JN, Buus NH, Christensen KL, Vase H, Bertelsen JB, et al. Renal sympathetic denervation in treatment resistant essential hypertension. A sham-controlled, double-blinded randomized trial (ReSET trial). Journal of the American College of Cardiology 2015;66:B41. [Google Scholar]

[CD011499-bib-0050] Mathiassen ON, Vase H, Bech JN, Christensen KL, Buus NH, Schroeder AP, et al. Renal denervation in treatment-resistant essential hypertension. A randomized, SHAM-controlled, double-blinded 24-h blood pressure-based trial. Journal of Hypertension 2016;34:1639–47. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0051] NCT01459900. Renal sympathectomy in treatment resistant essential hypertension: a sham controlled randomized trial [Renal sympathectomy in treatment resistant essential hypertension: a sham controlled randomized trial]. clinicaltrials.gov/show/NCT01459900 (first received 2011).

[CD011499-bib-0052] Peters CD, Mathiassen ON, Vase H, Norgaard BJ, Christensen KL, Schroeder AP, et al. The effect of renal denervation on arterial stiffness, central blood pressure and heart rate variability in treatment resistant essential hypertension: a substudy of a randomized sham-controlled double-blinded trial (the ReSET trial). Blood Pressure 2017;26:366-80. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0053] Beus E, Jager RL, Beeftink MM, Sanders MF, Spiering W, Vonken EJ, et al. Salt intake and blood pressure response to percutaneous renal denervation in resistant hypertension. Journal of Clinical Hypertension 2017;19:1125-33. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0054] Jager RL, Beus E, Beeftink MMA, Sanders MF, Vonken EJ, Voskuil M, et al. Impact of Medication Adherence on the Effect of Renal Denervation: The SYMPATHY Trial. Hypertension 2017;69(4):678-84. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0055] NCT01850901. Renal sympathetic denervation as a new treatment for therapy resistant hypertension [Renal sympathetic denervation as a new treatment for therapy resistant hypertension - a multicenter randomized controlled trial]. clinicaltrials.gov/show/NCT01850901 (first received 2013).

[CD011499-bib-0056] Vink EE, De Beus E, De Jager RL, Voskuil M, Spiering W, Vonken EJ, et al. The effect of renal denervation added to standard pharmacologic treatment versus standard pharmacologic treatment alone in patients with resistant hypertension: rationale and design of the SYMPATHY trial. American Heart Journal 2014;167:308-14.e3. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0057] Boehm M, Schlaich MP, Krum H, Schmieder RE, Sobotka P, Esler MD. One-year pooled outcomes following renal sympathetic denervation in patients with resistant hypertension: from the SYMPLICITY HTN-2 trial. European Heart Journal 2012;33:770. [Google Scholar]

[CD011499-bib-0058] Esler M, Krum H, Schmieder R, Bohm M. Renal sympathetic denervation for treatment of resistant hypertension: Two-year update from the SYMPLICITY HTN-2 randomized controlled trial. Journal of the American College of Cardiology 2013;1:E1386. [Google Scholar]

[CD011499-bib-0059] Esler MD, Bohm M, Sievert H, Rump CL, Schmieder RE, Krum H, et al. Catheter-based renal denervation for treatment of patients with treatment-resistant hypertension: 36-month results from the SYMPLICITY HTN-2 randomized clinical trial. European Heart Journal 2014;35:1752-9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0060] Esler MD, Krum H, Schlaich M, et al. Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the SYMPLICITY HTN-2 randomized, controlled trial. Orvosi Hetilap 2014;155(21):843. [DOI: 10.1556/OH.2014.21M] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0061] Esler MD, Krum H, Schlaich M, Schmieder R, Bohm M, Sobotka P. Renal sympathetic denervation for treatment of resistant hypertension: One year results from the SYMPLICITY HTN-2 randomized controlled trial. Journal of the American College of Cardiology 2012;1:E1705. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0062] Esler MD, Krum H, Schlaich M, Schmieder RE, Bohm M, Sobotka PA, et al. Renal sympathetic denervation for treatment of drug-resistant hypertension: one-year results from the SYMLICITY HTN-2 randomized, controlled trial. Circulation 2012;126:2976-82. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0063] Esler MD, Krum H, Schlaich M, Schmieder RE, Bohm M, Sobotka PA, et al. SYMPLICITY HTN-2: international, multicenter, prospective, randomized, controlled trial of endovascular selective renal sympathetic denervation for the treatment of hypertension. Circulation 2010;122:2220. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0064] Esler MD, Krum H, Schlaich MP, Schmieder RE, Boehm M, Sobotka P. Catheter-based renal sympathetic denervation in patients with resistant hypertension: 18-month follow-up of the SYMPLICITY HTN-2 trial. European Heart Journal 2012;33:181. [Google Scholar]

[CD011499-bib-0065] Esler MD, Krum H, Schlaich MP, Schmieder RE, Bohm M. Persistent and safe blood pressure lowering effects of renal artery denervation: three-year follow-up from the SYMPLICITY HTN-2 trial. Journal of the American College of Cardiology 2013;1:B19. [Google Scholar]

[CD011499-bib-0066] Murray E, Henry K, Marcus S, Roland S, Michael B. Long-term follow-up of catheter-based renal denervation in patients with treatment resistant hypertension: the SYMPLICITY HTN-2 trial. Journal of Clinical Hypertension 2013;15(Suppl 1):28. [Google Scholar]

[CD011499-bib-0067] NCT00888433. Renal denervation in patients with uncontrolled hypertension (SYMPLICITY HTN-2) [Renal denervation in patients with uncontrolled hypertension (SYMPLICITY HTN-2)]. clinicaltrials.gov/show//NCT00888433 (first received 2009).

[CD011499-bib-0068] Symplicity HTN-2 Investigators, Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (the SYMPLICITY HTN-2 Trial): a randomised controlled trial. Lancet 2010;376(9756):1903-9. [DOI: 10.1016/S0140-6736(10)62039-9] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0069] Ukena C, Mahfoud F, Ewen S, Kindermann I, Boehm M. Cardiorespiratory response to exercise after renal sympathetic denervation in resistant hypertension. Cardiology (Switzerland) 2013;125:158. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0070] Ukena C, Mahfoud F, Kindermann I, Barth C, Lenski M, Kindermann M, et al. Cardiorespiratory response to exercise after renal sympathetic denervation in patients with resistant hypertension. Journal of the American College of Cardiology 2011;58:1176-82. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0071] Ukena C, Mahfoud F, Kindermann I, Kindermann M, Brandt MC, Hoppe U, et al. Cardiorespiratory response to exercise after renal sympathetic denervation in patients with resistant hypertension. European Heart Journal 2011;32:960. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0072] Bakris GL, Townsend RR, Flack JM, Brar S, Cohen SA, D'Agostino, et al. 12-month blood pressure results of catheter-based renal artery denervation for resistant hypertension: the SYMPLICITY HTN-3 trial. Journal of the American College of Cardiology 2015;65:1314-21. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0073] Bakris GL, Townsend RR, Liu M, Cohen SA, D'Agostino R, Flack JM, et al. Impact of renal denervation on 24-hour ambulatory blood pressure: results from SYMPLICITY HTN-3. Journal of the American College of Cardiology 2014;64:1071-8. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0074] Bhatt DL, Bakris GL. Long-term (24-month) blood pressure results of catheter-based renal artery denervation: SYMPLICITY HTN-3 randomized controlled trial. Journal of the American College of Cardiology 2015;1:B38-9. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0075] Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, et al. A controlled trial of renal denervation for resistant hypertension. New England Journal of Medicine 2014;370:1393-401. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0076] Bhatt DL, Kandzari DE, O'Neill WW. A controlled trial of renal denervation for resistant hypertension. Journal of Vascular Surgery 2014;60:266. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0077] Divison JA, Escobar CC, Segui DM. Controlled clinical trial on renal denervation in resistant hypertension. Semergen 2014;40:345-6. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0078] Flack J, Bakris GL, Kandzari D, Katzen BT, Leon M, Mauri L, et al. SYMPLICITY HTN-3: outcomes in the African-American and Non-African American populations. Journal of the American College of Cardiology 2014;1:B119-20. [Google Scholar]

[CD011499-bib-0079] Flack JM, Bhatt DL, Kandzari DE, Brown D, Brar S, Choi J, et al. An analysis of the blood pressure and safety outcomes to renal denervation in African Americans and Non-African Americans in the SYMPLICITY HTN-3 trial. Journal of the American Society of Hypertension 2015;9:769-79. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0080] Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M, et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. European Heart Journal 2015;36:219-27. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0081] Kandzari DE, Bhatt DL, Sobotka PA, O'Neill WW, Esler M, Flack JM, et al. Catheter-based renal denervation for resistant hypertension: rationale and design of the SYMPLICITY HTN-3 trial. Clinical Cardiology 2012;35:528-35. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0082] Kario K, Bakris G, Pocock S, Fahy M, Bhatt DL. Changes in nocturnal blood pressure post-renal denervation: comparison of treatment versus control groups in SYMPLICITY HTN-3. European Heart Journal 2019;40 Suppl 1:664. [Google Scholar]

[CD011499-bib-0083] Kario K, Bakris GL, Bhatt D. Preferential reduction in morning/nocturnal hypertension by renal denervation for drug-resistant hypertension: a new ABPM analysis of SYMPLICITY HTN-3 and HTN-Japan. Journal of Hypertension 2015;33 Suppl 1:e52. [Google Scholar]

[CD011499-bib-0084] Kario K, Bhatt DL, Brar S, Cohen SA, Fahy M, Bakris GL. Effect of catheter-based renal denervation on morning and nocturnal blood pressure: insights from SYMPLICITY HTN-3 and SYMPLICITY HTN-Japan. Hypertension 2015;66:1130-7. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0085] Kario K, Bhatt DL, Townsend R, Flack J, Negoita M, Oparil S, et al. Potential reduction in office and nocturnal blood pressure after renal denervation in patients with obstructive sleep apnea: A subgroup analysis of SYMPLICITY HTN-3. European Heart Journal 2015;36:186. [Google Scholar]

[CD011499-bib-0086] NCT01418261. SYMPLICITY HTN-3 renal denervation in patients with uncontrolled hypertension [Renal denervation in patients with uncontrolled hypertension (SYMPLICITY HTN-3)]. clinicaltrials.gov/show/NCT01418261 (first received 2011).

[CD011499-bib-0087] Pekarskiy S, Baev A, Mordovin V, Sitkova E, Semke G, Ripp T, et al. Failure of renal denervation in SYMPLICITY HTN-3 is a predictable result of anatomically inadequate operative technique and not the true limitations of the technology. Journal of Hypertension 2015;33 Suppl 1:e108. [Google Scholar]

[CD011499-bib-0088] NCT01366625. Renal denervation in patients with resistant hypertension and obstructive sleep apnea [Effects of renal denervation on blood pressure and clinical course of obstructive sleep apnea in patients with resistant hypertension]. clinicaltrials.gov/show/NCT01366625 (first received 2011).

[CD011499-bib-0089] Warchol-Celinska E, Prejbisz A, Kadziela J, Florczak E, Januszewicz M, Michalowska I, et al. Renal Denervation in Resistant Hypertension and Obstructive Sleep Apnea: Randomized Proof-of-Concept Phase II Trial. Hypertension 2018;72:381-90. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0090] Warchol-Celinska E, Prejbisz A, Kadziela J, Sliwinski P, Plywaczewski R, Florczak E, et al. Effect of renal denervation on blood pressure levels and clinical course of obstructive sleep apnea in patients with resistant hypertension-3 months outcomes of randomized trial. European Heart Journal 2016;37 Suppl 1:793. [Google Scholar]

[CD011499-bib-0091] Warchol E, Prejbisz A, Kadziela J, Florczak E, Kabat M, Sliwinski P, et al. The impact of renal sympathetic denervation on office and ambulatory blood pressure levels in patients with true resistant hypertension and obstructive sleep apnea: the interim analysis. European Heart Journal 2014;35:231. [Google Scholar]

[CD011499-bib-0092] Ahmed H, Neuzil P, Skoda J, Petru J, Sediva L, Schejbalova M, et al. Renal sympathetic denervation using an irrigated radiofrequency ablation catheter for the management of drug-resistant hypertension. JACC. Cardiovascular Interventions 2012;5:758-65. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0093] Ahmed H, Miller MA, Dukkipati SR, Cammack S, Koruth JS, Gangireddy S, et al. Adjunctive renal sympathetic denervation to modify hypertension as upstream therapy in the treatment of atrial fibrillation (H-FIB) study: clinical background and study design. Journal of Cardiovascular Electrophysiology 2013;24:503-9. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0094] Azizi M, Schmieder RE, Mahfoud F, Weber M, Daemen J, Davies J, et al. Radiance-HTN solo: A multicenter, randomized, shamcontrolled study of renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications. Journal of Hypertension 2018;36 Suppl 1:e238. [Google Scholar]

[CD011499-bib-0095] Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Lobo MD, et al. Six-month results of treatment-blinded medication titration for hypertension control following randomization to endovascular ultrasound renal denervation or a sham procedure in the RADIANCE-HTN SOLO trial. Circulation 2019;139:2542-2553. [DOI: 10.1161/CIRCULATIONAHA.119.040451] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0096] Azizi M, Schmieder R, Mahfoud F, Weber M, Daemen J, Lobo M, et al. Treatment-Blinded Medication Titration for Hypertension Control Following Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure. Journal of the American College of Cardiology 2019;73(9 Suppl 1):1034. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0097] Baev A, Pekarskiy S, Mordovin V, Ripp T, Falkovskaya A, Lichikaki V, et al. A distal mode of renal denervation in segmental branches of renal artery versus conventional main trunk therapy: a double blind randomized controlled study in patients with resistant hypertension. Journal of the american college of cardiology 2017;18 Suppl 1:B86. [Google Scholar]

[CD011499-bib-0098] Bohm M, Kandzari D, Townsend R, Mahfoud F, Weber M, Fahy M, et al. Spyral HTN-OFF MED trial: Changes in office and ambulatory heart rate. Journal of Hypertension 2018;36 Suppl 1:e23-e24. [Google Scholar]

[CD011499-bib-0099] Bohm M, Mahfoud F, Townsend RR, Kandzari DE, Pocock S, Ukena C, et al. Ambulatory heart rate reduction after catheter-based renal denervation in hypertensive patients not receiving anti-hypertensive medications: data from SPYRAL HTN-OFF MED, a randomized, sham-controlled, proof-of-concept trial. European Heart Journal 2019;40(9):743-51. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0100] Bohm M, Townsend RR, Kario K, Kandzari D, Mahfoud F, Weber MA, et al. Correction to: rationale and design of two randomized sham controlled of catheterbased renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTNOFF MED Pivotal) and presence (SPYRAL HTNON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design. Clinical Research in Cardiology 2020;109:653. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0101] Bohm M, Townsend RR, Kario K, Kandzari D, Mahfoud F, Weber MA, et al. Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design. Clinical Research in Cardiology 2020;109:289-302. [DOI: 10.1007/s00392-020-01595-z] [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0102] Bohm M, Kario K, Kandzari DE, Mahfoud F, Weber MA, Schmieder RE, et al T. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet 2020;395:1444-51. [DOI: 10.1016/S0140-6736(20)30554-7] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0103] Bosch A, Schmid A, Ott C, Kannenkeril D, Karg MV, Ditting T, et al. Copeptin levels in patients with treatment-resistant hypertension before and 6 months after renal denervation. American Journal of Hypertension 2020;33(2):182-9. [DOI: 10.1093/ajh/hpz155] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0104] Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M, et al. Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. Journal of the American College of Cardiology 2012;59:901-9. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0105] Brandt MC, Reda S, Mahfoud F, Lenski M, Bohm M, Hoppe UC. Effects of renal sympathetic denervation on arterial stiffness and central hemodynamics in patients with resistant hypertension. Journal of the American College of Cardiology 2012;60:1956-65. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0106] Chen S, Kiuchi MG, Acou WJ, Derndorfer M, Wang J, Li R, et al. Feasibility of catheter ablation renal denervation in "mild" resistant hypertension. Journal of Clinical Hypertension 2017;19(4):361-8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0107] Chen H, Ji M, Zhang Y, Xu Y, Qiao L, Shen L, et al. Correction to: efficiency and safety of renal denervation via cryoablation (Cryo-RDN) in Chinese patients with uncontrolled hypertension: study protocol for a randomized controlled trial. Trials 2019;20:770. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0108] Chen H, Ji M, Zhang Y, Xu Y, Qiao L, Shen L, et al. Efficiency and safety of renal denervation via cryoablation (Cryo-RDN) in Chinese patients with uncontrolled hypertension: study protocol for a randomized controlled trial. Trials 2019;20:653. [DOI: 10.1186/s13063-019-3693-9] [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0109] ChiCTR-ONC-12002901. Transcatheter renal denervation for patients with resistant hypertension [Transcatheter renal denervation for patients with resistant hypertension]. Http://www.chictr.org.cn/showproj.aspx? Proj=6653 2012.

[CD011499-bib-0110] ChiCTR-ONC-13003231. Noninvasive renal sympathetic denervation by high-intensity focused ultrasound (HIFU) in patients with refractory hypertension [Noninvasive renal sympathetic denervation by high-intensity focused ultrasound (HIFU) in patients with refractory hypertension]. http://www.chictr.org.cn/showproj.aspx?proj=6328 2013.

[CD011499-bib-0111] ChiCTR-TNC-12002900. A comprehensive assessment of the cardiovascular effects of transcatheter renal sympathetic nerve denervation [A comprehensive assessment of the cardiovascular effects of transcatheter renal sympathetic nerve denervation]. http://www.chictr.org.cn/showproj.aspx?proj=6654 2012.

[CD011499-bib-0112] Courand PY, Pereira H, Gosse P, Bobrie G, Delsart P, Mounier-Vehier C, et al. Presence of aortic abdominal calcifications in patients with resistant hypertension and bp response in the renal denervation for hypertension (DENERHTN) trial. Journal of Hypertension 2016;34 Suppl 2:e172. [Google Scholar]

[CD011499-bib-0113] Courand PY, Pereira H, Del Giudice C, Gosse P, Monge, MBobrie, G et al. Abdominal Aortic Calcifications Influences the Systemic and Renal Hemodynamic Response to Renal Denervation in the DENERHTN (Renal Denervation for Hypertension) Trial. Journal of the American Heart Association 2017;6(10):10. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0114] Jager RL, Van Maarseveen EM, Bots ML, Blankestijn PJ. Medication adherence in patients with apparent resistant hypertension: findings from the SYMPATHY trial. British Journal of Clinical Pharmacology 2018;84(1):18-24. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0115] De Jager R, Van Maarseveen E, Bots M, Blankestijn P. Medication adherence in patients with apparent resistant hypertension: Findings from the sympathy trial. Nephrology Dialysis Transplantation 2017;32 Suppl 3:iii47. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0116] Dimitriadis K, Tsioufis K, Kasiakogias A, Kalos TH, Liatakis G, Nikolopoulou L, et al. Effects of multielectrode renal denervation on sympathetic nerve activity and insulin resistance in metabolic syndrome. Journal of Hypertension 2017;35 Suppl 2:e148. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0117] DRKS00005865. Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension. http://www.drks.de/DRKS00005865 2014.

[CD011499-bib-0118] DRKS00006405. Safety and efficacy study investigating the effects of catheter-based renal denervation on different organ systems in patients with increased sympathetic activity. http://www.drks.de/DRKS00006405 2014.

[CD011499-bib-0119] DRKS00006420. Rapid renal sympathetic denervation for resistant hypertension using the oneshot™ ablation system. http://www.drks.de/DRKS00006420 2014. [DOI] [PubMed]

[CD011499-bib-0120] DRKS00006493. A randomized safety and efficacy study investigating the effects of catheter-based renal denervation in patients after renal transplantation. http://www.drks.de/DRKS00006493 2015.

[CD011499-bib-0121] Eikelis N, Hering D, Marusic P, Duval J, Hammond LJ, Walton AS, et al. The effect of renal denervation on plasma adipokine profile in patients with treatment resistant hypertension. Frontiers in Physiology 2017;8:369. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0122] NCT01836146. International first-in-human study of the EnligHTN generation 2 system in patients with drug-resistant uncontrolled hypertension (EnligHTN III). clinicaltrials.gov/show/NCT01836146 (first received 2013).

[CD011499-bib-0123] Esler M, Krum H, Schlaich M, Bohm M, Schmieder RE. Renal denervation via catheter-based delivery of radiofrequency energy significantly reduces blood pressure in subjects with severe treatment-resistant hypertension: long-term results from the SYMPLICITY-HTN clinical trials. Circulation 2013;128(S22):A14747. [Google Scholar]

[CD011499-bib-0124] Ewen S, Mahfoud F, Linz D, Poss J, Cremers B, Kindermann I, et al. Effects of renal sympathetic denervation on exercise blood pressure, heart rate, and capacity in patients with resistant hypertension. Hypertension 2014;63:839-45. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0125] Elmula MF, Hoffmann P, Fossum E, Brekke M, Gjonnaess E, Hjornholm U, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension after witnessed intake of medication before qualifying ambulatory blood pressure. Hypertension 2013;62:526-32. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0126] Fengler K, Hollriegel R, Okon T, Stiermaier T, Rommel KP, Blazek S, et al. Ultrasound-based renal sympathetic denervation for the treatment of therapy-resistant hypertension: a single-center experience. Journal of Hypertension 2018;35(6):1310-7. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0127] Forssell C, Bjarnegard N, Nystrom FH. A pilot study of perioperative external circumferential cryoablation of human renal arteries for sympathetic denervation. Vascular specialist international 2020;36:151-7. [DOI: 10.5758/vsi.200023] [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0128] Grassi G, Seravalle G, Brambilla G, Trabattoni D, Cuspidi C, Corso R, et al. Blood pressure responses to renal denervation precede and are independent of the sympathetic and baroreflex effects. Hypertension 2015;65:1206-16. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0129] Hamdidouche I, Gosse P, Cremer A, Lorthioir A, Delsart P, Courand PY, et al. Clinic versus ambulatory blood pressure in resistant hypertension: impact of antihypertensive medication nonadherence: a post hoc analysis the DENERHTN study. Hypertension 2019;74:1096-1103. [DOI: 10.1161/HYPERTENSIONAHA.119.13520] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0130] Hering D, Lambert EA, Marusic P, Ika-Sari C, Walton AS, Krum H, et al. Renal nerve ablation reduces augmentation index in patients with resistant hypertension. Journal of Hypertension 2013;31:1893-900. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0131] Kampmann U, Mathiassen ON, Christensen KL, Buus NH, Bjerre M, Moller N, et al. The effect of renal denervation on insulin sensitivity, blood pressure, and inflammatory markers in treatment-resistant hypertensive patients. Diabetes 2016;65 Suppl 1:A121. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0132] Kandzari DE, Kario K, Mahfoud F, Cohen SA, Pilcher G, Pocock S, et al. The SPYRAL-HTN global clinical trial program: rationale and design for studies of renal denervation in the absence (SPYRAL-HTN OFF-MED) and presence (SPYRAL-HTN ON-MED) of antihypertensive medications. American Heart Journal 2016;171:82-91. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0133] Kandzari DE, Bohm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet 2018;391:2346-55. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0134] Karbasi-Afshar R, Noroozian R, Shahmari A, Saburi A. The effect of renal arteries sympathectomy on refractory hypertension. Tehran University Medical Journal 2013;71:179-84. [Google Scholar]

[CD011499-bib-0135] Kario K, Bohm M, Mahfoud F, Townsend RR, Weber MA, Patel M, et al. Twenty-four-hour ambulatory blood pressure reduction patterns after renal denervation in the SPYRAL HTN-OFF MED trial. Circulation 2018;138(15):1602-4. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0136] Kario K, Yamamoto E, Tomita H, Okura T, Saito S, Ueno T, et al. Sufficient and persistent blood pressure reduction in the final long-term results from SYMPLICITY HTN-Japan - safety and efficacy of renal denervation at 3 years. Circulation Journal 2019;83(3):622-9. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0137] Kario K, Weber MA, Bohm M, Townsend RR, Mahfoud F, Schmieder RE, et al. Effect of renal denervation in attenuating the stress of morning surge in blood pressure: post-hoc analysis from the SPYRAL HTN-ON MED trial. Clinical research in cardiology 2020;110(5):725-731. [DOI: 10.1007/s00392-020-01718-6] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0138] Kario K, Boehm M, Townsend R, Mahfoud F, Pocock S, Weber M, et al. Twenty-four-hour ambulatory blood pressure reduction profiles of renal denervation in the spyral HTN-OFF MED trial. Journal of the American College of Cardiology 2018;71(11 Suppl 1):no pagination. [Google Scholar]

[CD011499-bib-0139] Katholi R, Esler M, Krum H, Rocha-Singh K, Schlaich M, Bohm M, et al. Pooled 3-year SYMPLICITY HTN-1 and SYMPLICITY HTN-2 results and diabetes subgroup analysis. JACC: Cardiovascular Interventions 2014;1:S50. [Google Scholar]

[CD011499-bib-0140] Kjeldsen SE, Narkiewicz K, Oparil S, Hedner T. Renal denervation in treatment-resistant hypertension: Oslo RDN, SYMPLICITY HTN-3 and INSPiRED randomized trials. Blood Pressure 2014;23:135-7. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0141] Krum H, Schlaich MP, Sobotka PA, Bohm M, Mahfoud F, Rocha-Singh K, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the SYMPLICITY HTN-1 study. Lancet 2014;383:622-9 . [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0142] Li Y, Nawabi AQ, Feng Y, Dai Q, Ma G, Liu N. Safety and efficacy of a new renal denervation catheter in hypertensive patients in the absent of antihypertensive medications: a pilot study. International Journal Of Hypertension 2019;2019:7929706. [DOI: 10.1155/2019/7929706] [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0143] Li LY, Lu TJ, Zhang H, Deng WM, Duan QX, Gao JQ, et al. Renal sympathetic denervation for treatment of resistant hypertension using a 5 F microtube-irrigated ablation catheter. Academic journal of second military medical university 2019;40:1263-9. [DOI: 10.16781/j.0258-879x.2019.11.1263] [DOI] [Google Scholar]

[CD011499-bib-0144] Lobo M, Saxena M, Jain A, Walters D, Pincus M, Montarello J, et al. Safety and performance of the EnligHTN renal denervation system in patients with uncontrolled hypertension and chronic kidney disease: 12 month results from the EnligHTN II study. Journal of Hypertension 2015;33(1):e363. [Google Scholar]

[CD011499-bib-0145] Lurz P, Kresoja KP, Rommel KP, Von Roeder M, Besler C, Lucke C, et al. Changes in stroke volume after renal denervation: insight from cardiac magnetic resonance imaging. Hypertension 2020;75:707-13. [DOI: 10.1161/HYPERTENSIONAHA.119.14310] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0146] Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, et al. Effect of renal sympathetic denervation on glucosmetabolism in patients with resistant hypertension. Internist 2011;52:36. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0147] Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation 2011;123:1940-6. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0148] Mahfoud F, Cremers B, Janker J, Link B, Vonend O, Ukena C, et al. Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension. Hypertension 2012;60:419-24. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0149] Mahfoud F, Ukena C, Schmieder RE, Cremers B, Rump LC, Vonend O, et al. Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension. Circulation 2013;128(2):132-40. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0150] Mahfoud F, Urban D, Teller D, Linz D, Stawowy P, Hassel JH, et al. Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial. European Heart Journal 2014;35:2224-31b. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0151] Mahfoud F, Kandzari DE, Kario K, Pocock S, Schmieder RE, Townsend RR, et al. Changes in plasma renin activity after renal denervation in the SPYRAL HTN-off med trial. Hypertension 2019;74 Suppl 1:no pagination. [DOI: 10.1161/hyp.74.suppl_1.109] [DOI] [Google Scholar]

[CD011499-bib-0152] Mahfoud F, Renkin J, Sievert H, Bertog S, Ewen S, Bohm M, et al. Alcohol-mediated renal denervation using the peregrine system infusion catheter for treatment of hypertension. JACC: cardiovascular interventions 2020;13:471-84. [DOI: 10.1016/j.jcin.2019.10.048] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0153] Mahfoud F, Mancia G, Schmieder R, Narkiewicz K, Ruilope L, Schlaich M, et al. Renal denervation in high-risk patients with hypertension. Journal of the American College of Cardiology 2020;75(23):2879-88. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0154] Mahfoud F, Townsend R, Kandzari D, Kario K, Schmieder R, Tsioufis K, et al . TCT Connect-417 impact of renal denervation on plasma renin activity and relationship of baseline plasma renin activity to blood pressure lowering response to renal denervation in the SPYRAL HTN-OFF MED pivotal trial. Journal of the American College of Cardiology 2020;76 (17 Suppl ):B179. [Google Scholar]

[CD011499-bib-0155] NCT01117025. Combined treatment of resistant hypertension and atrial fibrillation. clinicaltrials.gov/show/NCT01117025 (first received 2010).

[CD011499-bib-0156] NCT01465724. Renal sympathetic denervation for treatment of metabolic syndrome associated hypertension (Metabolic Syndrome study). clinicaltrials.gov/show/NCT01465724 (first received 2013).

[CD011499-bib-0157] NCT01583881. Renal denervation in patients with heart failure with normal LV ejection fraction. clinicaltrials.gov/show/NCT01583881 (first received 2014).

[CD011499-bib-0158] NCT01631370. The effects of renal sympathetic denervation on insulin sensitivity in patients with resistant essential hypertension. clinicaltrials.gov/show/NCT01631370 (first received 2012).

[CD011499-bib-0159] NCT01635998. Adjunctive renal sympathetic denervation to modify hypertension as upstream therapy in the treatment of atrial fibrillation. clinicaltrials.gov/show/NCT01635998 (first received 2012). [DOI] [PubMed]

[CD011499-bib-0160] NCT01687725. Renal denervation in treatment resistant hypertension. clinicaltrials.gov/show/NCT01687725 (first received 2012).

[CD011499-bib-0161] NCT01733901. Renal sympathetic denervation as secondary prevention for patients after percutaneous coronary intervention. clinicaltrials.gov/show/NCT01733901 (first received 2012).

[CD011499-bib-0162] NCT01814111. Safety and effectiveness study of percutaneous catheter-based sympathetic denervation of the renal arteries in patients with hypertension and paroxysmal atrial fibrillation. clinicaltrials.gov/show/NCT01814111 (first received 2012).

[CD011499-bib-0163] NCT01848314. The effect of renal denervation on renal flow in humans. clinicaltrials.gov/show/NCT01848314 (first received 2013).

[CD011499-bib-0164] NCT01873352. Renal artery denervation in addition to catheter ablation to eliminate atrial fibrillation. clinicaltrials.gov/show/NCT01873352 (first received 2013).

[CD011499-bib-0165] NCT01888315. Influence of catheter-based renal denervation in diseases with increased sympathetic activity. clinicaltrials.gov/show/NCT01888315 (first received 2012).

[CD011499-bib-0166] NCT01897545. The role of renal denervation in improving outcomes of catheter ablation in patients with atrial fibrillation and arterial hypertension. clinicaltrials.gov/show/NCT01897545 (first received 2012).

[CD011499-bib-0167] NCT01901549. Renal denervation in patients after acute coronary syndrome. clinicaltrials.gov/show/NCT01901549 (first received 2013).

[CD011499-bib-0168] NCT01907828. A feasibility study to evaluate the effect of concomitant renal denervation and cardiac ablation on AF recurrence. clinicaltrials.gov/show/NCT01907828 (first received 2013).

[CD011499-bib-0169] NCT01932450. Radiofrequency ablation for ADPKD blood pressure and disease progression control. clinicaltrials.gov/show/NCT01932450 (first received 2013).

[CD011499-bib-0170] NCT02016573. Renal denervation for uncontrolled hypertension. clinicaltrials.gov/show/NCT02016573 (first received 2013).

[CD011499-bib-0171] NCT02057224. Metabolic and cardiovascular effects of renal denervation. clinicaltrials.gov/show/NCT02057224 (first received 2014).

[CD011499-bib-0172] NCT02115100. Treatment of atrial fibrillation in patients by pulmonary vein isolation, renal artery denervation or both. clinicaltrials.gov/show/NCT02115100 (first received 2014).

[CD011499-bib-0173] NCT02115230. Transcatheter renal denervation in heart failure with normal left ventricular ejection fraction - a safety and efficacy study of irrigated radiofrequency catheter. clinicaltrials.gov/show/NCT02115230 (first received 2014).

[CD011499-bib-0174] NCT02155790. The Peregrine study: a safety and performance study of renal denervation. clinicaltrials.gov/show/NCT02155790 (first received 2014).

[CD011499-bib-0175] NCT02164435. Effects of renal sympathetic denervation on the cardiac and renal functions in patients with drug-resistant hypertension through MRI evaluation (RDN). clinicaltrials.gov/show/NCT02164435 (first received 2014).

[CD011499-bib-0176] NCT02272920. PCI and renal denervation in hypertensive patients with acute coronary syndromes. clinicaltrials.gov/show/NCT02272920 (first received 2014).

[CD011499-bib-0177] NCT02559882. Testing effectiveness of renal denervation in patients with therapy-resistant hypertension. clinicaltrials.gov/show/NCT02559882 (first received 2015).

[CD011499-bib-0178] Baev, APekarskiy, SMordovin, VRipp, TFalkovskaya, ALichikaki, V et al. A distal mode of renal denervation in segmental branches of renal artery versus conventional main trunk therapy: a double blind randomized controlled study in patients with resistant hypertension. Journal of the american college of cardiology 2017;18 Suppl 1:B86. [Google Scholar]

[CD011499-bib-0179] NCT02667912. Distal renal denervation. clinicaltrials.gov/show/NCT02667912 (first received 2016).

[CD011499-bib-0180] Pekarskiy, SBaev, AMordovin, VSemke, GRipp, TFalkovskaya, A et al. Distal renal denervation performed mainly in segmental branches of renal artery versus conventional mode of the intervention: A randomized controlled trial in patients with resistant hypertension. European Heart Journal 2016;37 Suppl 1:78. [Google Scholar]

[CD011499-bib-0181] NCT03261375. A clinical trial to evaluate safety and efficacy of a renal denervation system in treatment of hypertension. ClinicalTrials.gov/show/NCT03261375 2017.

[CD011499-bib-0182] NCT03465917. Physiological study of the efficacy and mechanistic effects of alcohol renal denervation. ClinicalTrials.gov/show/NCT03465917 2018.

[CD011499-bib-0183] NCT03511313. Renal denervation with sterile irrigated deflectable ablation catheter used in renal artery in primary hypertension. ClinicalTrials.gov/show/NCT03511313 2018.

[CD011499-bib-0184] DENEX renal denervation in patients With uncontrolled hypertension: safety study. clinicaltrials.gov/show/NCT04248530.

[CD011499-bib-0185] Renal denervation in chronic kidney disease - RDN-CKD study. https://clinicaltrials.gov/show/NCT04264403 (first received 11 February 2020).

[CD011499-bib-0186] DENEX renal denervation in patients with hypertension on no or 1-3 antihypertensive medications (DENEX HTN-KORAS). clinicaltrials.gov/show/NCT04307836 (first received 13 March 2020).

[CD011499-bib-0187] SPYRAL DYSTAL clinical study. clinicaltrials.gov/show/NCT04311086 (first received 17 March 2020).

[CD011499-bib-0188] DENEX renal denervation in patients with hypertension on no antihypertensive medications. clinicaltrials.gov/show/NCT04535050 (first received 1 September 2020).

[CD011499-bib-0189] Palionis D, Berukstis A, Misonis N, Ryliskyte L, Celutkiene J, Zakarkaite D, et al . Could careful patient selection for renal denervation warrant a positive effect on arterial stiffness and left ventricular mass reduction? Acta cardiologica 2016;71:173-83. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0190] Pekarskiy S, Baev A, Mordovin V, Semke G, Ripp T, Falkovskaya A, et al. Distal renal denervation performed mainly in segmental branches of renal artery versus conventional mode of the intervention: A randomized controlled trial in patients with resistant hypertension. European Heart Journal 2016;37 Suppl 1:78. [Google Scholar]

[CD011499-bib-0191] Pekarskiy S. TCT CONNECT-416 powerful antihypertensive effect of anatomically optimized distal renal denervation 3 years after the procedure according to a double-blind randomized controlled study. Journal of the American College of Cardiology 2020;76(17 Suppl ):B178-9. [DOI: 10.1016/j.jacc.2020.09.441] [DOI] [Google Scholar]

[CD011499-bib-0192] Persu A, Renkin J, Hochul M, Wojakowski W, Bohm M, Mahfoud F, et al. Chemical renal denervation with alcohol - Long term results from the peregrine post-market study. Journal of Hypertension 2018;36 Suppl 1:e123. [Google Scholar]

[CD011499-bib-0193] Petrov I, Tasheva I, Garvanski I, Tankov Z, Simova I. Comparison of standard renal denervation procedure versus novel distal and branch vessel procedure with brachial arterial access. Cardiovascular Revascularization Medicine 2019;20(1):38-42. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0194] Pokushalov E, Romanov A, Artyomenko S, Turov A, Shirokova N, Karaskov A. Renal denervation and pulmonary vein isolation in patients with drug resistant hypertension and symptomatic atrial fibrillation. European Heart Journal 2012;33:382. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0195] Pokushalov E, Romanov A, Artyomenko S, Turov A, Shirokova N, Karaskov A. Renal denervation and pulmonary vein isolation in patients with drug resistant hypertension and symptomatic atrial fibrillation. Heart Rhythm 2012;1:S172. [Google Scholar]

[CD011499-bib-0196] Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, et al. A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. Journal of the American College of Cardiology 2012;60:1163-70. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0197] Pokushalov E, Romanov A, Katritsis D, Artyomenko S, Bayramova S, Losik D, et al. The role of renal denervation in improving outcomes of catheter ablation in patients with atrial fibrillation and moderate resistant or resistant hypertension. Journal of the American College of Cardiology 2014;1:A280. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0198] Pokushalov E, Romanov A, Katritsis D, Artyomenko S, Bayramova S, Losik D, et al. Renal denervation for improving outcomes of catheter ablation in patients with atrial fibrillation and hypertension: early experience. European Heart Journal 2014;35:434-5. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0199] Pokushalov E, Romanov A, Katritsis DG, Artyomenko S, Bayramova S, Losik D, et al. Renal denervation for improving outcomes of catheter ablation in patients with atrial fibrillation and hypertension: early experience. Heart Rhythm 2014;11:1131-8. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0200] Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, et al. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet 2018;391:2335-45. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0201] NCT03614260. The RADIANCE II pivotal study: a study of the recor medical paradise system in stage II hypertension. ClinicalTrials.gov/show/NCT03614260 (first received 3 August 2018);(first received 10 August 2005).

[CD011499-bib-0202] NCT01520506. Rapid renal sympathetic denervation for resistant hypertension (RAPID). clinicaltrials.gov/show/NCT01520506 (first received 2012).

[CD011499-bib-0203] NCT01355055. Sympathetic activity and renal denervation (ReD). clinicaltrials.gov/show/NCT01355055 (first received 2011).

[CD011499-bib-0204] NCT02392351. Renal denervation using the Vessix Renal Denervation system for the treatment of hypertension (REDUCE HTN:REINFORCE). clinicaltrials.gov/show/NCT02392351 (first received 2015).

[CD011499-bib-0205] Ripp T, Ryabova T, Pekarskiy S, Mordovin V, Buharova E, Anfinogenova YA, et al. Cardiac function, structure, and speckle-tracking echocardiography-derived parameters after distal and conventional renal denervation: a double-blind randomized study. European heart journal 2019;40:665. [DOI: 10.1093/eurheartj/ehz748.0031] [DOI] [Google Scholar]

[CD011499-bib-0206] NTR4384. Feasibility of electrical mapping and stimulation of renal arteries in patients undergoing renal denervation. https://trialregister.nl/trial/4239 2014.

[CD011499-bib-0207] NCT02642445. Renal sympathetic denervation from the adventitia on hypertension (RSDAH). clinicaltrials.gov/show/NCT02642445 (first received 2015).

[CD011499-bib-0208] Sanders M, De Jager R, Bots M, Lobo M, Blankestijn P. Renal denervation in hypertensive patients not on blood pressure lowering drugs. Journal of Hypertension 2016;34 Suppl 2:e94-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0209] Saxena M, Lobo MD, O'Brien BO, Toennes C, Gertner SW, Dawood M, et al. Phase II randomized sham-controlled study of renal denervation for subjects with uncontrolled hypertension-WAVE IV. Journal of Human Hypertension 2017;31 (10):679. [Google Scholar]

[CD011499-bib-0210] Saxena M, Shour T, Shah M, Wolff CB, Julu POO, Kapil V, et al. Attenuation of splanchnic autotransfusion following noninvasive ultrasound renal denervation: a novel marker of procedural success. Journal of the American Heart Association 2018;7(12):12. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0211] Scalise F, Sole A, Singh G, Sorropago A, Sorropago G, Ballabeni C, et al. Renal denervation in patients with end-stage renal disease and resistant hypertension on long-term haemodialysis. Journal of Hypertension 2020;38(5):936-42. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0212] Schmieder RE, Ott C, Toennes S, Gertner M, Dawood O, Saxena M, et al. Phase II randomized sham-controlled study of renal denervation for subjects with uncontrolled hypertension-wave IV. Journal of Hypertension 2017;35 Suppl 2:e21. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0213] Schmieder RE, Ott C, Toennes SW, Bramlage P, Gertner M, Dawood O, et al. Phase II randomized sham-controlled study of renal denervation for individuals with uncontrolled hypertension - WAVE IV. Journal of Hypertension 2018;36(3):680-9. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0214] Shipman KE. A controlled trial of renal denervation for resistant hypertension. Annals of Clinical Biochemistry 2014;51:621. [Google Scholar]

[CD011499-bib-0215] Shugushev Z, Maximkin DA, Chepurnoy A, Safonova O, Faibushevich A. Sympathetic renal denervation in patients with refractory arterial hypertension: 2-years follow-up. European Heart Journal 2019;21(Suppl 1):562. [DOI: 10.1093/eurheartj/ehz745.0954] [DOI] [Google Scholar]

[CD011499-bib-0216] Shugushev Z, Maximkin D, Alexandr C, Faibushevich A, Safonova O, Mambetov A. TCT-605 sympathetic renal denervation in patients with refractory arterial hypertension: 2-year follow-up. Journal of the American College of Cardiology 2019;74(13 Suppl ):B594. [DOI: 10.1016/j.jacc.2019.08.718] [DOI] [Google Scholar]

[CD011499-bib-0217] Sievert H, Kipshidze NN, Kipiani K, Kipiani V, Mukhuradze T, Wholey M. First clinical experience with neurotropic agents for treatment of sympathetic hypertension. Journal of the American College of Cardiology 2014;1(11):B119. [PubMed] [Google Scholar]

[CD011499-bib-0218] Sitkova ES, Mordovin VF, Pekarsky SE, Ripp TM, Falkovskaya AYu, Lichikaki VA, et al. Distal renal denervation: cardioprotection in patients with resistant hypertension. Cardiovascular therapy and prevention (russian federation) 2020;19:no pagination. [DOI: 10.15829/1728-8800-2019-2225] [DOI] [Google Scholar]

[CD011499-bib-0219] NCT02439749. Global clinical study of renal denervation with the SYMPLICITY SPYRAL™ multi-electrode renal denervation system in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED). clinicaltrials.gov/show/NCT02439749 (first received 12 May 2015).

[CD011499-bib-0220] NCT02439775. Global clinical study of renal denervation with the SYMPLICITY SPYRAL™ multi-electrode renal denervation system in patients with uncontrolled hypertension on standard medical therapy (SPYRAL HTN-ON MED). clinicaltrials.gov/show/NCT02439775 (first received 12 May 2015).

[CD011499-bib-0221] Stoiber L, Mahfoud F, Zamani SM, Lapinskas T, Bohm M, Ewen S, et al. Renal sympathetic denervation restores aortic distensibility in patients with resistant hypertension: data from a multi-center trial. Clinical Research in Cardiology 2018;107(8):642-52. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0222] SYMPLICITY HTN Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension 2011;57:911-7. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0223] NCT02064764. Renal nerve denervation in patients with hypertension and paroxysmal and persistent atrial fibrillation (SYMPLICITY AF). clinicaltrials.gov/show/NCT02064764 (first received 17 February 2014).

[CD011499-bib-0224] NCT03503773. The TARGET BP OFF-MED trial. ClinicalTrials.gov/show/NCT03503773 (first received 20 April 2018).

[CD011499-bib-0225] Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet 2017;390:2160-70. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0226] Tsioufis C, Dimitriadis K, Kasiakogias A, Kalos T, Liatakis I, Koutra E, et al . Effects of multielectrode renal denervation on sympathetic nerve activity and insulin resistance in metabolic syndrome. Journal of Hypertension 2016;34 Suppl 2:e78. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0227] UMIN000012020. Study of renal sympathetic denervation with radiofrequency ablation catheter for resistant essential hypertension. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014034 2013.

[CD011499-bib-0228] Wage R, Patel H, Smith GC, Keegan J, Gatehouse P, Vassiliou V, et al. The utility of magnetic resonance imaging in a trial to assess the effect of renal denervation in heart failure with preserved ejection fraction. Journal of Cardiovascular Magnetic Resonance 2015;17(S1):T7. [Google Scholar]

[CD011499-bib-0229] Waksman R, Bakris GL, Steinvil A, Garcia-Garcia HM, Debruin V, Jolivette D, et al. SYMPLICITY HTN-3 screen failure patient cohort analysis. European Heart Journal 2016;37 Suppl 1:230. [Google Scholar]

[CD011499-bib-0230] NCT02029885. Sham controlled study of renal denervation for subjects with uncontrolled hypertension (WAVE IV). clinicaltrials.gov/show/NCT02029885 (first received 8 January 2014).

[CD011499-bib-0231] NCT02480517. Wave VI feasibility study: Phase II randomized sham controlled study of renal denervation for untreated Stage I and II hypertension. clinicaltrials.gov/show/NCT02480517 (first received 24 June 2015).

[CD011499-bib-0232] Weber MA, Kandzari D, Bohm M, Mahfoud F, Kario K, Walton T, et al. Adherence to antihypertensive drugs: Insights from the spyral HTN trials and implications for hypertension trial design. Hypertension 2018;72 Suppl 1:no pagination. [Google Scholar]

[CD011499-bib-0233] Weber MA, Kirtane AJ, Weir MR, Radhakrishnan JD, Berk T, Mendelsohn M, et al. The REDUCE HTN: REINFORCE: randomized, sham-controlled trial of bipolar radiofrequency renal denervation for the treatment of hypertension. JACC. Cardiovascular interventions 2020;13(4):461-70. [DOI: 10.1016/j.jcin.2019.10.061] [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0234] Witkowski A, Prejbisz A, Florczak E, Kadziela J, Sliwinski P, Bielen P, et al. Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension 2011;58:559-65. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0235] Xiang C, Xu YL, Liu ZJ, Yan PY, Gao JQ, Gao BL. Effects of catheter-based renal sympathetic denervation at different segments of the renal artery on resistant hypertension. Experimental and Clinical Cardiology 2014;20:145-56. [Google Scholar]

[CD011499-bib-0236] Xu YL, Liu ZJ, Jin HG, Gao JQ, Yan PY, Zhang WQ, et al. Effect of ablation sites in catheter-based renal sympathetic denervation on anti-hypertension results in patients with resistant hypertension. Academic Journal of Second Military Medical University 2014;35:191-4. [Google Scholar]

[CD011499-bib-0237] Yin Y, Chen W, Ling Z, Xu Y, Liu Z, Su L, et al. Preliminary effects of renal sympathetic denervation with saline irrigated catheter on systolic function in patients with heart failure - a feasibility report from the swan-HF pilot study. Circulation 2013;128(S22):A17684. [Google Scholar]

[CD011499-bib-0238] Zhang ZH, Yang K, Jiang FL, Zeng LX, Jiang WH, Wang XY. The effects of catheter-based radiofrequency renal denervation on renal function and renal artery structure in patients with resistant hypertension. Journal of Clinical Hypertension 2014;16:599-605. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0239] NCT01874470. Renal denervation by Allegro system in patients with resistant hypertension. clinicaltrials.gov/show/NCT01874470 (first received 2013).

[CD011499-bib-0240] NCT01522430. Denervation of renal sympathetic activity and hypertension study. clinicaltrials.gov/show/NCT01522430 (first received 2012).

[CD011499-bib-0241] NCT01903187. Multi-center, randomized, single-blind, sham controlled clinical investigation of renal denervation for uncontrolled hypertension. clinicaltrials.gov/show/NCT01903187 (first received 2013).

[CD011499-bib-0242] NCT02102126. Effect of renal denervation on arterial stiffness and haemodynamics in patients with uncontrolled hypertension (ENSURE). clinicaltrials.gov/show/NCT02102126 (first received 2014).

[CD011499-bib-0243] NCT02002585. Renal protection using sympathetic denervation in patients with chronic kidney disease (Kidney protection study - KPS Study). clinicaltrials.gov/show/NCT02002585 (first received 2013).

[CD011499-bib-0244] NCT01848275. Full length versus proximal renal arteries ablation. clinicaltrials.gov/show/NCT01848275 (first received 2011).

[CD011499-bib-0245] NCT01918111. Effects of renal denervation for resistant hypertension on exercise diastolic function and regression of atherosclerosis and the evaluation of new methods predicting a successful renal sympathetic denervation (RENEWAL-EXERCISE, -REGRESS, and -PREDICT trial from RENEWAL RDN Registry). clinicaltrials.gov/show/NCT01918111 (first received 2013).

[CD011499-bib-0246] NCT01968785. Renal denervation in patients with uncontrolled blood pressure. clinicaltrials.gov/show/NCT01968785 (first received 2013).

[CD011499-bib-0247] NCT02021019. Renal denervation to improve outcomes in patients with end-stage renal disease. clinicaltrials.gov/show/NCT02021019 (first received 2014).

[CD011499-bib-0248] NCT02346045. Effect of renal denervation in end stage renal disease with resistant hypertension. clinicaltrials.gov/show/NCT02346045 (first received 2014).

[CD011499-bib-0249] NCT02444442. The Australian SHAM controlled clinical trial of renal denervation in patients with resistant hypertension (AUSHAM RDN-01). clinicaltrials.gov/show/NCT02444442 (first received 2015).

[CD011499-bib-0250] NCT02608632. High frequency guided renal artery denervation for improving outcome of renal ablation procedure. clinicaltrials.gov/show/NCT02608632 (first received 2015).

[CD011499-bib-0251] Liu Z, Shen L, Huang W, Zhao X, Fang W, Wang C, et al. Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial. BMJ Open 2017;7(9):e015672. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0252] NTR3444. Endovascular renal sympathetic denervation versus spironolactone in treatment-resistant hypertension: a randomized, multicentric study (RRSS trial). www.trialregister.nl/trialreg/admin/rctview.asp?TC=3444 (first received 2012).

[CD011499-bib-0253] NCT01895140. A study of renal denervation in patients with treatment resistant hypertension. clinicaltrials.gov/ct2/show/NCT01895140 (first received 2013).

[CD011499-bib-0254] Azizi M, Basile J, Daemen J, Davies J, Francis D, Kirtane A, et al. The "rADIANCE-HTN" clinical study: a two-cohort study design to evaluate the effectiveness of the paradise renal denervation system in patients with hypertension. Journal of the American Society of Hypertension 2016;10(4 Suppl):e39. [Google Scholar]

[CD011499-bib-0255] NCT02649426. A study of the ReCor Medical Paradise system in clinical hypertension (RADIANCE-HTN). clinicaltrials.gov/show/NCT02649426 (first received 2016).

[CD011499-bib-0256] NCT01939392. Rapid renal sympathetic denervation for resistant hypertension using the OneShot renal denervation system II (RAPID II). clinicaltrials.gov/show/NCT01939392 (first received 2013).

[CD011499-bib-0257] NCT01865240. Renal denervation for resistant hypertension. clinicaltrials.gov/show/NCT01865240 (first received 2013).

[CD011499-bib-0258] NCT01617551. Effect of renal denervation on no-mediated regulation of salt and water excretion, vasoactive hormones and tubular transport proteins in patients with resistant hypertension (RENO). clinicaltrials.gov/show/NCT01617551 (first received 2012).

[CD011499-bib-0259] NCT01785732. Renal sympathetic denervation and insulin sensitivity (RENSYMPIS study). clinicaltrials.gov/show/NCT01785732 (first received 2013).

[CD011499-bib-0260] NCT01762488. Renal denervation in treatment resistant hypertension, a double-blind randomized controlled trial (ReSET-2). clinicaltrials.gov/show/NCT01762488 (first received 2013).

[CD011499-bib-0261] NCT01737138. Safety and effectiveness study of percutaneous catheter-based renal sympathetic denervation in patients with chronic kidney disease and resistant hypertension. clinicaltrials.gov/show/NCT01737138 (first received 2012).

[CD011499-bib-0262] NCT03758196. Renal sympathetic denervation from the adventitia on resistant hypertension (RSDARH）. clinicaltrials.gov/show/NCT03758196 (first received 29 November 2018 ).

[CD011499-bib-0263] NCT01713270. Safety and effectiveness study of percutaneous catheter-based renal sympathetic denervation in patients with drug-resistant hypertension and symptomatic atrial fibrillation. clinicaltrials.gov/show/NCT01713270 (first received 2012).

[CD011499-bib-0264] Qiu M, Yin Y, Shan Q. Renal sympathetic denervation versus antiarrhythmic drugs for drug-resistant hypertension and symptomatic atrial fibrillation (RSDforAF) trial: study protocol for a randomized controlled trial. Trials 2013;14:168. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0265] NCT01972139. Renal denervation in patients with uncontrolled hypertension - SYMPLICITY HTN-4. clinicaltrials.gov/show/NCT01972139 (first received 2013).

[CD011499-bib-0266] Agasthi P, Shipman J, Arsanjani R, Ashukem M, Girardo ME, Yerasi C, et al. Renal denervation for resistant hypertension in the contemporary era: a systematic review and meta-analysis. Scientific Reports 2019;9(1):6200. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0267] Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation 2008;117(25):e510-26. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0268] Davis MI, Filion KB, Zhang D, Eisenberg MJ, Afilalo J, Schiffrin EL, et al. Effectiveness of renal denervation therapy for resistant hypertension: a systematic review and meta-analysis. Journal of the American College of Cardiology 2013;16(3):231-41. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0269] Esler M. Renal denervation: not as easy as it looks. Science Translational Medicine 2015;7(285):285fs18. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0270] Fadl Elmula M, Feng Y-M, Jacobs L, Larstorp AC, Kjeldsen SE, Pers A, European Network COordinating research on Renal Denervation (ENCOReD). Sham or no sham control: that is the question in trials of renal denervation for resistant hypertension. A systematic meta-analysis. Blood Pressure 2017;26(4):195-203. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0271] GRADEpro Guideline Development Tool. Version (accessed prior to 25 October 2021). Hamilton (ON): McMaster University (developed by Evidence Prime, Inc.), 2015. www.guidelinedevelopment.org.

[CD011499-bib-0272] Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924-6. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0273] Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557-60. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0274] Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1.

[CD011499-bib-0275] Huan Y, Cohen DL. Renal denervation: a potential new treatment for severe hypertension. Clinical Cardiology 2013;36(1):10-4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0276] Judd E, Calhoun DA. Apparent and true resistant hypertension: definition, prevalence and outcomes. Journal of Human Hypertension 2014;28(8):463-8. [DOI: 10.1038/jhh.2013.140] [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0277] Kandzari DE, Bhatt DL, Brar S, Devireddy CM, Esler M, Fahy M, et al. Predictors of blood pressure response in the SYMPLICITY HTN-3 trial. European Heart Journal 2015;36(4):219-27. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0278] Leong KT, Walton A, Krum H. Renal sympathetic denervation for the treatment of refractory hypertension. Annual Review of Medicine 2014;65:349-65. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0279] Myat A, Redwood SR, Qureshi AC, Spertus JA, Williams B. Resistant hypertension. BMJ 2012;345:e7473. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0280] Nakagawa T, Hasegawa Y, Uekawa K, Ma M, Katayama T, Sueta D, et al. Renal denervation prevents stroke and brain injury via attenuation of oxidative stress in hypertensive rats. Journal of the American Heart Association 2013;2(5):e000375. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0281] Katayama T, Sueta D, Kataoka K, Hasegawa Y, Koibuchi N, Toyama K, et al. Long-term renal denervation normalizes disrupted blood pressure circadian rhythm and ameliorates cardiovascular injury in a rat model of metabolic syndrome. Journal of the American Heart Association 2013;2(4):e000197. [DOI] [PMC free article] [PubMed] [Google Scholar]

[CD011499-bib-0282] Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

[CD011499-bib-0283] Sakakura K, Ladich E, Cheng Q, Otsuka F, Yahagi K, Fowler DR, et al. Anatomic assessment of sympathetic peri-arterial renal nerves in man. Journal of the American College of Cardiology 2014;64(7):635-43. [DOI] [PubMed] [Google Scholar]

[CD011499-bib-0284] Giuseppe Coppolino, Anna Pisano, Laura Rivoli, Davide Bolignano. Renal denervation for resistant hypertension.. Review Cochrane Database Syst Rev. 2017;21(2):CD011499. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Renal denervation for resistant hypertension

Anna Pisano

Luigi Francesco Iannone

Antonio Leo

Emilio Russo

Giuseppe Coppolino

Davide Bolignano

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Summary of findings 1. Summary of findings.

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

1.

Included studies

Excluded studies

Risk of bias in included studies

2.

3.

Allocation

Blinding

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

Primary outcomes

Non‐fatal cardiovascular events

1.1. Analysis.

1.2. Analysis.

1.3. Analysis.

All‐cause mortality

Hospitalisation

1.4. Analysis.

Quality of life

Secondary outcomes

24‐hour ambulatory blood pressure monitoring (ABPM)

1.5. Analysis.

1.6. Analysis.

Daytime ABPM

1.7. Analysis.

1.8. Analysis.