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. 2014 Jun 26;2014:0608.

Diabetes: treating hypertension

Sandeep Vijan 1
PMCID: PMC4072092  PMID: 24967882

Abstract

Introduction

Between 2007 and 2010, the age-adjusted prevalence of hypertension in US adults with diabetes was 59%, more than double the prevalence in those without diabetes. Major cardiac events occur in approximately 5% of people with diabetes and untreated hypertension each year, and the risk is higher in those with other risk factors, such as diabetic nephropathy.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of different blood pressure targets in people with diabetes and hypertension? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 10 studies that met our inclusion criteria.

Conclusions

In this systematic review, we present information relating to the effectiveness and safety of the following intervention: more intensive (lower) blood pressure targets versus less intensive (higher) targets in people with diabetes and hypertension.

Key Points

The age-adjusted prevalence of hypertension in US adults with diabetes is 59%, more than double the prevalence in those without diabetes.

  • Major cardiac events occur in approximately 5% of people with diabetes and untreated hypertension each year, and the risk is higher in those with other risk factors, such as diabetic nephropathy.

Most studies enrolled participants with type 2 diabetes.

Early trials of blood pressure lowering in people with diabetes and hypertension, typically with systolic blood pressure targets of approximately 140–150 mmHg, reduced cardiovascular events and mortality in people with diabetes and hypertension.

Results from studies with intensive (lower) systolic blood pressure targets (e.g., 120–130 mmHg) are inconsistent. In general, cardiovascular benefit appears to diminish, and the risk of treatment-related adverse effects increases, with intensive management. It is, therefore, difficult to specify precise blood pressure goals for people with diabetes and hypertension.

We don't know whether more intensive (lower) blood pressure targets improve microvascular outcomes compared with less intensive (higher) targets.

One large RCT found that targeting a systolic blood pressure of <120 mmHg in people with type 2 diabetes did not reduce cardiovascular mortality or cardiovascular events compared with a target of <140 mmHg.

Few studies systematically report the adverse effects of treatment to reduce blood pressure in people with diabetes.

About this condition

Definition

Hypertension in diabetes is classically defined as a systolic blood pressure of 140 mmHg or greater or a diastolic blood pressure of 90 mmHg or greater. Hypertension is divided into three stages. Pre-hypertension is a systolic blood pressure of 120 mmHg to 139 mmHg or a diastolic blood pressure of 80 mmHg to 89 mmHg. Stage 1 hypertension is a systolic blood pressure of 140 mmHg to 159 mmHg or diastolic blood pressure of 90 mmHg to 99 mmHg. Stage 2 hypertension is a systolic blood pressure of 160 mmHg or greater or a diastolic blood pressure of 100 mmHg or greater. However, guidelines now suggest that drug therapy should be instituted in any person with diabetes and hypertension, regardless of stage. This review focuses on adults with diabetes with stage 1 or 2 hypertension, but with no diagnosis of CHD, diabetic retinopathy, or nephropathy. The control of hypertension in people with diabetic retinopathy and those with diabetic nephropathy are described in separate reviews.

Incidence/ Prevalence

Hypertension is highly prevalent among people with diabetes. It is about 1.5 to 3.0 times more common in people with type 2 diabetes than in the age-matched general population. Between 2007 and 2010, the age-adjusted prevalence of hypertension in US adults with diabetes was 59%, more than double the prevalence in those without diabetes. About 30% of people with type 1 diabetes eventually develop hypertension, usually after they develop diabetic nephropathy. The prevalence of hypertension varies depending on the population studied (see Aetiology).

Aetiology/ Risk factors

The cause of hypertension is multifactorial, complex, and not fully understood. In the general population, there are several major risk factors for hypertension; specific risk factors are not clearly different in the diabetic population. Age is the predominant factor; data suggest that prevalence increases with age. People with at least one parent with hypertension are about twice as likely to develop hypertension. African-American people have a 7% to 10% increase in prevalence compared with non-Hispanic white people from the US. Obese people also have greater risk: for each unit increase in BMI, the prevalence increases by about 1.0% to 1.5%. Insulin resistance is associated with development of hypertension.

Prognosis

Untreated hypertension in people with diabetes is associated with high rates of cardiovascular disease (such as MI, heart failure, and stroke) and microvascular disease (such as renal disease [including albuminuria, renal insufficiency, and end-stage renal disease] and diabetic retinopathy). In the placebo groups of major trials of hypertension control in type 2 diabetes, major cardiac events occurred in about 4% to 6% of people annually, and were substantially higher in populations with additional risk factors such as diabetic nephropathy.

Aims of intervention

To reduce cardiovascular and microvascular morbidity and mortality in people with diabetes, while minimising adverse effects of interventions.

Outcomes

Cardiovascular mortality; cardiovascular events (non-fatal); nephropathy; retinopathy; quality of life; and adverse effects, including hypoglycaemia, hyperglycaemia, dizziness, falls, increase in cardiac events (MI), impaired cognitive functioning (confusion, reduced concentration, memory problems).

Methods

Clinical Evidence search and appraisal October 2013. The following databases were used to identify studies for this systematic review: Medline 1966 to October 2013, Embase 1980 to October 2013, and The Cochrane Database of Systematic Reviews 2013, issue 9 (1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) Database. We also searched for retractions of studies included in the review. Titles and abstracts identified by the initial search, run by an information specialist, were first assessed against predefined criteria by an evidence scanner. Full texts for potentially relevant studies were then assessed against predefined criteria by an evidence analyst. Studies selected for inclusion were discussed with an expert contributor. All data relevant to the review were then extracted by an evidence analyst. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in English language, at least single-blinded, and containing at least 100 individuals (at least 50 per arm) of whom at least 80% were followed up. Minimum length of follow-up is 2 years. We included studies consisting of populations of adults (18 years and over) with type 1 and type 2 diabetes with hypertension but with no pre-existing diagnosis of coronary heart disease. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We included RCTs and systematic reviews of RCTs where harms of an included intervention were assessed, applying the same study design criteria for inclusion as we did for benefits. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Diabetes: treating hypertension.

Important outcomes Cardiovascular events, Cardiovascular mortality, Nephropathy, Quality of life, Retinopathy
Studies (Participants) Outcome Comparison Type of evidence Quality Consistency Directness Effect size GRADE Comment
What are the effects of different blood pressure targets in people with diabetes and hypertension?
2 (6234) Cardiovascular mortality More intensive (lower) blood pressure targets versus less intensive (higher) blood pressure targets 4 –1 –1 0 0 Low Quality point deducted for inclusion of a non-blinded trial; consistency point deducted for inconsistent results depending on analysis performed
5 (8351) Cardiovascular events More intensive (lower) blood pressure targets versus less intensive (higher) blood pressure targets 4 –1 –1 –1 0 Very low Quality point deducted for incomplete reporting of results; consistency point deducted for inconsistent evidence of beneficial effect of having a lower blood pressure target; directness point deducted for composite outcome in 3 RCTs
2 (at least 3444) Nephropathy More intensive (lower) blood pressure targets versus less intensive (higher) blood pressure targets 4 –1 –1 –1 0 Very low Quality point deducted for incomplete reporting of results; consistency point deducted for inconsistent evidence of beneficial effect of having a lower blood pressure target; directness point deducted for unclear outcome
2 (5014) Retinopathy More intensive (lower) blood pressure targets versus less intensive (higher) blood pressure targets 4 –1 0 –1 0 Low Quality point deducted for incomplete reporting of results; directness point deducted for unclear outcome
Open in a new tab

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Low-quality evidence

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 evidence

Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

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BMJ Clin Evid. 2014 Jun 26;2014:0608.

More intensive (lower) blood pressure targets versus less intensive (higher) blood pressure targets

Summary

Most studies enrolled participants with type 2 diabetes.

Early trials of blood pressure lowering in people with diabetes and hypertension, typically with systolic blood pressure targets of approximately 140–150 mmHg, reduced cardiovascular events and mortality in people with diabetes and hypertension.

Results from studies with intensive (lower) systolic blood pressure targets (e.g., 120–130 mmHg) are inconsistent. In general, cardiovascular benefit appears to diminish, and the risk of treatment-related adverse effects increases, with intensive management. It is, therefore, difficult to specify precise blood pressure goals for people with diabetes and hypertension.

We don't know whether more intensive (lower) blood pressure targets improve microvascular outcomes compared with less intensive (higher) targets.

One large RCT found that targeting a systolic blood pressure of <120 mmHg in people with type 2 diabetes did not reduce cardiovascular mortality or cardiovascular events compared with a target of <140 mmHg.

Few studies systematically report the adverse effects of treatment to reduce blood pressure in people with diabetes.

Benefits and harms

More intensive (lower) blood pressure targets versus less intensive (higher) blood pressure targets:

We found three systematic reviews (search dates 2002, 2010, and 2012) identifying five RCTs comparing intensive blood pressure targets with less intensive targets. The first RCT conducted a prespecified subgroup analysis in people with diabetes. We found two subsequent follow-up reports of RCTs.

Cardiovascular mortality

More intensive (lower) compared with less intensive (higher) blood pressure targets A target of less-than or equal to 80 mmHg diastolic may be more effective than a target of less-than or equal to 90 mmHg diastolic at reducing cardiovascular mortality, and a target of less-than or equal to 80 mmHg may be more effective than a target of less-than or equal to 85 mmHg diastolic. We don't know whether a target of less-than or equal to 85 mmHg diastolic is more effective than a target of less-than or equal to 90 mmHg at reducing cardiovascular mortality, or whether a target of <120 mmHg systolic is more effective than a target of <140 mmHg (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Cardiovascular mortality

RCT
3-armed trial 		1501 people; diabetes type unspecified; mean age 61.5 years; mean blood pressure 170/105 mmHg
In review
Subgroup analysis		 Cardiovascular mortality
11.1/1000 person-years with target diastolic blood pressure less-than or equal to 90 mmHg
3.7/1000 person-years with target diastolic blood pressure less-than or equal to 80 mmHg
RR 3.0
95% CI 1.28 to 7.08
P = 0.016 		Moderate effect size more intensive (lower) blood pressure target

RCT
3-armed trial 		1501 people; diabetes type unspecified; mean age 61.5 years; mean blood pressure 170/105 mmHg
In review
Subgroup analysis		 Cardiovascular mortality
11.2/1000 person-years with target diastolic blood pressure less-than or equal to 85 mmHg
3.7/1000 person-years with target diastolic blood pressure less-than or equal to 80 mmHg
RR 3.0
95% CI 1.29 to 7.13 		Moderate effect size more intensive (lower) blood pressure target

RCT
3-armed trial 		1501 people; diabetes type unspecified; mean age 61.5 years; mean blood pressure 170/105 mmHg
In review
Subgroup analysis		 Cardiovascular mortality
11.1/1000 person-years with target diastolic blood pressure less-than or equal to 90 mmHg
11.2/1000 person years with target diastolic blood pressure less-than or equal to 85 mmHg
RR 0.99
95% CI 0.54 to 1.82 		Not significant

Systematic review		 4733 people with type 2 diabetes; mean age 62.2 years; mean blood pressure 139/76 mmHg; 34% had CVD at baseline Cardiovascular mortality 4.7 years
60/2363 (3%) with target systolic blood pressure <120 mmHg
58/2371 (2%) with target systolic blood pressure <140 mmHg
HR 1.04
95% CI 0.72 to 1.50 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Cardiovascular events

More intensive (lower) compared with less intensive (higher) blood pressure targets A target of less-than or equal to 80 mmHg diastolic may be more effective than a target of less-than or equal to 90 mmHg at reducing cardiovascular events (composite outcome), and a target of <150/85 mmHg may be more effective than <180/105 mmHg. We don't know whether a target of less-than or equal to 115 mmHg systolic is more effective than a target of less-than or equal to 130 mmHg at reducing cardiovascular events, or whether a target of <120 mmHg systolic is more effective than a target of <140 mmHg (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Cardiovascular events

RCT
3-armed trial 		1501 people; diabetes type unspecified; mean age 61.5 years; mean blood pressure 170/105 mmHg
In review
Subgroup analysis		 Major cardiovascular event rates
11.9/1000 person-years with target diastolic blood pressure less-than or equal to 80 mmHg
24.4/1000 person-years with target diastolic blood pressure less-than or equal to 90 mmHg
RR 0.49
95% CI 0.29 to 0.81
No significant difference reported for MI or stroke (see Further information on studies) 		Moderate effect size more intensive (lower) blood pressure target

RCT
3-armed trial 		1501 people; diabetes type unspecified; mean age 61.5 years; mean blood pressure 170/105 mmHg
In review
Subgroup analysis		 Major cardiovascular event rates
with target diastolic blood pressure less-than or equal to 85 mmHg
with target diastolic blood pressure less-than or equal to 90 mmHg
Absolute results not reported
RR 1.32
95% CI 0.84 to 2.06
No significant difference reported for MI or stroke (see Further information on studies) 		Not significant

RCT
3-armed trial 		1501 people; diabetes type unspecified; mean age 61.5 years; mean blood pressure 170/105 mmHg
In review
Subgroup analysis		 Major cardiovascular event rates
with target diastolic blood pressure less-than or equal to 80 mmHg
with target diastolic blood pressure less-than or equal to 85 mmHg
Absolute results not reported
RR 1.56
95% CI 0.91 to 2.67
No significant difference reported for MI or stroke (see Further information on studies) 		Not significant

RCT		 1148 people with newly diagnosed type 2 diabetes; mean age 56 years; mean blood pressure 160/94 mmHg
In review 		Any cardiovascular outcome 8.4 years
with target blood pressure <150/85 mmHg
with target blood pressure <180/105 mmHg
Absolute results not reported
RR 0.66
P = 0.019
CI not reported 		Small effect size more intensive (lower) blood pressure target

RCT		 470 people with type 2 diabetes; mean age 58 years; blood pressure 155/98 mmHg
In review 		Cardiovascular end points
with target diastolic blood pressure 75 mmHg
with target diastolic blood pressure 80–89 mmHg
Absolute results not reported
Reported as not significant
P value not reported
No significant difference reported for MI or stroke (see Further information on studies) 		Not significant

RCT		 4733 people with type 2 diabetes; mean age 62.2 years; mean blood pressure 139/76 mmHg; 34% had CVD at baseline Cardiovascular events 4.7 years (mean follow-up)
208/2363 (1.9%/year) with target systolic blood pressure <120 mmHg
237/2371 (2.1%/year) with target systolic blood pressure <140 mmHg
HR 0.88
95% CI 0.74 to 1.06
P = 0.20
No significant difference reported for specific cardiovascular outcomes, except stroke (see Further information on studies) 		Not significant

Systematic review		 499 patients with type 2 diabetes MI
2/252 (1%) with target systolic blood pressure less-than or equal to 115 mmHg
2/247 (1%) with target systolic blood pressure less-than or equal to 130 mmHg
OR 0.98
95% CI 0.14 to 7.00 		Not significant

Systematic review		 499 patients with type 2 diabetes Stroke
1/252 (0.39%) with target systolic blood pressure less-than or equal to 115 mmHg
3/247 (1%) with target systolic blood pressure less-than or equal to 130 mmHg
OR 0.36
95% CI 0.05 to 2.56 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Nephropathy

More intensive (lower) compared with less intensive (higher) blood pressure targets We don't know whether a target of 75 mmHg diastolic and a target of 80 to 89 mmHg differ in effectiveness at reducing nephropathy. A target of <120 mmHg systolic may be marginally more effective than a target of <140 mmHg at reducing the rate of nephropathy; however, results were inconsistent and dependent upon outcome and analysis performed (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Nephropathy

RCT		 470 people with type 2 diabetes; mean age 58 years; blood pressure 155/98 mmHg
In review 		Progression of renal disease
with target diastolic blood pressure 75 mmHg
with target diastolic blood pressure 80–89 mmHg
Absolute results not reported
RR 1.38
95% CI 0.84 to 2.27 		Not significant

Systematic review		 470 patients with type 2 diabetes
Further report of reference 		Nephropathy
16/237 (7%) with target diastolic blood pressure 75 mmHg
23/233 (10%) with target diastolic blood pressure 80–90 mmHg
OR 0.66
95% CI 0.35 to 1.28 		Not significant

RCT		 4733 people with type 2 diabetes; mean age 62.2 years; mean blood pressure 139/76 mmHg; 34% had CVD at baseline
Further report of reference 		Microalbuminuria 4.7 years
20.8% with target systolic blood pressure <120 mmHg
25.0% with target systolic blood pressure <140 mmHg
Absolute results not reported
HR 0.84
95% CI 0.72 to 0.97
P = 0.019 		Small effect size more intensive (lower) blood pressure target

RCT		 4733 people with type 2 diabetes; mean age 62.2 years; mean blood pressure 139/76 mmHg; 34% had CVD at baseline
Further report of reference 		Macroalbuminuria 4.7 years
5.7% with target systolic blood pressure <120 mmHg
7.1% with target systolic blood pressure <140 mmHg
Absolute results not reported
HR 0.81
95% CI 0.63 to 1.03
P = 0.087 		Not significant

RCT		 4733 people with type 2 diabetes; mean age 62.2 years; mean blood pressure 139/76 mmHg; 34% had CVD at baseline
Further report of reference 		Renal failure 4.7 years
2.6% with target systolic blood pressure <120 mmHg
2.7% with target systolic blood pressure <140 mmHg
Absolute results not reported
HR 1.00
95% CI 0.71 to 1.43
P = 0.991 		Not significant

Systematic review		 4733 people with type 2 diabetes; mean age 62.2 years; mean blood pressure 139/76 mmHg; 34% had CVD at baseline Nephropathy 4.7 years
143/2362 (6%) with target systolic blood pressure <120 mmHg
192/2371 (8%) with target systolic blood pressure <140 mmHg
OR 0.73
95% CI 0.59 to 0.92 		Small effect size more intensive (lower) blood pressure target
Open in a new tab

No data from the following reference on this outcome.

Retinopathy

More intensive (lower) compared with less intensive (higher) blood pressure targets We don't know whether a target of 75 mmHg diastolic and a target of 80 to 89 mmHg differ in effectiveness at reducing the rate of retinopathy. We don't know whether a target of <120 mmHg systolic is more effective at reducing the rate of retinopathy than a target of <140 mmHg (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Retinopathy

RCT		 470 people with type 2 diabetes; mean age 58 years; blood pressure 155/98 mmHg
In review 		Retinopathy
with target diastolic blood pressure 75 mmHg
with target diastolic blood pressure 80–89 mmHg
Absolute results not reported
RR 0.88
95% CI 0.68 to 1.15 		Not significant

RCT		 4733 people with type 2 diabetes; mean age 62.2 years; mean blood pressure 139/76 mmHg; 34% had CVD at baseline
Further report of reference 		Retinopathy 4.7 years
9.6% with target systolic blood pressure <120 mmHg
9.1% with target systolic blood pressure <140 mmHg
Absolute results not reported
HR 1.09
95% CI 0.90 to 1.32
P = 0.371 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT		 1148 people with newly diagnosed type 2 diabetes; mean age 56 years; mean blood pressure 160/94 mmHg
In review 		Hypoglycaemia
6% with target blood pressure <150/85 mmHg
4% with target blood pressure <180/105 mmHg
Absolute numbers not reported
Reported as not significant
P value not reported 		Not significant

RCT		 4734 people with type 2 diabetes; mean age 62.2 years; mean blood pressure 139/76 mmHg; 34% had CVD at baseline Dizziness
217/501 (44%) with target systolic blood pressure <120 mmHg
188/467 (40%) with target systolic blood pressure <140 mmHg
P = 0.36 		Not significant

RCT
3-armed trial 		1501 people; diabetes type unspecified; mean age 61.5 years; mean blood pressure 170/105 mmHg Adverse effects
with target diastolic blood pressure less-than or equal to 80 mmHg
with target diastolic blood pressure less-than or equal to 85 mmHg
with target diastolic blood pressure less-than or equal to 90 mmHg

Systematic review		 At least 37,736 people with type 2 diabetes Adverse effects
with target systolic blood pressure less-than or equal to 135 mmHg
with target systolic blood pressure less-than or equal to 140 mmHg

RCT		 499 patients with type 2 diabetes Adverse effects
with target systolic blood pressure less-than or equal to 115 mmHg
with target systolic blood pressure less-than or equal to 130 mmHg
4734 people with type 2 diabetes Adverse effects
with target systolic blood pressure <120 mmHg
with target systolic blood pressure <140 mmHg
Open in a new tab

No data from the following reference on this outcome.

Further information on studies

The blood pressures achieved were 140/81 mmHg in the less-than or equal to 80 mmHg target group, 141/83 mmHg in the less-than or equal to 85 mmHg target group, and 144/85 mmHg in the less-than or equal to 90 mmHg diastolic target group. Overall mortality: a systematic review reported this three-armed RCT and found no significant difference in overall mortality between the less-than or equal to 80 mmHg diastolic blood pressure target and the less intensive targets of less-than or equal to 85 mmHg (RR 0.59, 95% CI 0.33 to 1.06) or less-than or equal to 90 mmHg (RR 0.57, 95% CI 0.32 to 1.02). MI: a diastolic blood pressure target of less-than or equal to 80 mmHg did not significantly reduce the risk of MI compared with the less intensive targets of less-than or equal to 85 mmHg (RR 0.88, 95% CI 0.32 to 2.40) or less-than or equal to 90 mmHg (RR 0.50, 95% CI 0.20 to 1.23). Stroke: a diastolic blood pressure target of less-than or equal to 80 mmHg did not significantly reduce the risk of stroke compared with less intensive targets of less-than or equal to 85 mmHg (RR 0.93, 95% CI 0.43 to 2.01) or less-than or equal to 90 mmHg (RR 0.71, 95% CI 0.34 to 1.47). Adverse effects: side effects decreased from 16.9% at 3 months to 2.2% at final visit.

The blood pressures achieved were 144/82 mmHg in the <150/85 mmHg target group, and 154/87 mmHg in the <180/105 mmHg target group. Diabetes-related outcomes: The RCT found that the risk of any diabetes end point was significantly reduced in the intensive target group (cardiovascular end points plus renal failure, amputation, vitreous haemorrhage, retinal photocoagulation, blindness in one eye, or cataract extraction) compared with the non-intensive target group (50.9/1000 person-years with intensive target v 67.4/1000 person-years with non-intensive target; RR 0.76, 95% CI 0.62 to 0.92). The RCT also found that the risks of diabetes-related death (13.7/1000 person-years with intensive target v 20.3/1000 person-years with non-intensive target; RR 0.68, 95% CI 0.49 to 0.94) and microvascular end points (12.0/1000 person-years with intensive target v 19.2/1000 person-years with non-intensive target; RR 0.63, 95% CI 0.44 to 0.89) were significantly reduced in the intensive compared with the non-intensive target group.

The mean achieved blood pressure was 132/78 mmHg in the intensive group and 138/86 mmHg in the less intensive group. Overall mortality: the RCT documented a difference in overall mortality (6% with intensive target v 11% with less intensive target; P = 0.037), although the authors were unable to ascertain the reasons for this decline in mortality (e.g., there were no differences in any cardiovascular or microvascular mortality). MI: a systematic review found that a diastolic blood pressure target of 75 mmHg did not significantly reduce the risk of MI compared with a target of 80–89 mmHg (RR 0.80, 95% CI 0.44 to 1.46). Stroke: a diastolic blood pressure target of 75 mmHg did not significantly reduce the risk of stroke compared with a target of 80–89 mmHg (RR 0.83, 95% CI 0.38 to 1.82).

The review found that few studies reported serious adverse events (not otherwise specified). In those that did, intensive blood pressure targets (less-than or equal to 130 mmHg; less-than or equal to 135 mmHg) were associated with an increased likelihood of serious adverse events (OR 1.2, 95% CI 1.08 to 1.32; OR 1.4, 95% CI 1.19 to 1.64, respectively) compared with less intensive control (less-than or equal to 140 mmHg). There was significant heterogeneity in this analysis (I2 = 78.8%). Of note, this systematic review included 13 RCTs enrolling 37,736 patients, some of which were not included in the current review.

This systematic review reported abbreviated treatment-related adverse events from the ACCORD RCT. Adverse events from this RCT are reported elsewhere (see Further information on studies for reference).

The systolic blood pressures achieved were 119.3 mmHg in the intensive (<120 mmHg) group and 133.5 mmHg in the less intensive (<140 mmHg) group. The RCT found no differences in combined cardiovascular events, total mortality (HR 1.07, 95% CI 0.85 to 1.35), or cardiovascular mortality between groups. There was a statistically significant lower risk of stroke, both fatal (HR 0.59, 95% CI 0.39 to 0.89) and non-fatal (HR 0.63, 95% CI 0.41 to 0.96) in the intensive treatment arm; but in the aggregate analysis this was offset by trends towards increased overall cardiovascular mortality. A systematic review found that the intensive systolic blood pressure target (<120 mmHg) did not reduce the risk of MI compared with the less intensive target of <140 mmHg (RR 0.94, 95% CI 0.80 to 1.11). Adverse effects: hypotension (17/2362 [0.7%] v 1/2371 [0.04%]; P <0.001), bradycardia or arrhythmia (12/2362 [0.5%] v 3/2371 [0.13%]; P = 0.02), and hyperkalaemia (9/2362 [0.4%] v 1/2371 [0.04%]; P = 0.01) were significantly more common in the intensive treatment (<120 mmHg) group than the less intensive (<140 mmHg) group. The incidence of syncope (12/2362 [0.5%] v 5/2371 [0.21%]; P = 0.1), angioedema (6/2362 [0.3%] v 4/2371 [0.17%]; P = 0.55), renal failure (5/2362 [0.2%] v 1/2371 [0.04%]; P = 0.12), and end-stage renal disease or need for dialysis (59/2362 [2.5%] v 58/2371 [2.4%]; P = 0.93) did not differ between treatment groups.

Adverse events (not otherwise specified) related to blood pressure drugs were more common in the intensive systolic blood pressure target (less-than or equal to 115 mmHg) group than the less intensive (less-than or equal to 130 mmHg) group (67/252 [27%] v 38/247 [15%]; P = 0.002). The incidence of serious adverse events (not otherwise specified) related to blood pressure drugs did not differ significantly between intensive and less intensive treatment groups (4/252 [0.2%] v 1/247 [0.004%]; P = 0.18).

Reports microvascular outcomes from the ACCORD study.

Comment

Systolic blood pressure targets have only been shown to be effective in trials testing a target level of <150 mmHg; targeting this level has clear benefits. However, achieved blood pressures in studies showing benefit have been substantially lower than 150 mmHg (140 mmHg in 1 study and 144 mmHg in another). Thus, it is acceptable to conclude that a target of at least 140 mmHg is reasonable. A study examining more aggressive blood pressure lowering (systolic blood pressure target <120 mmHg v <140 mmHg) showed no effect on cardiovascular events or mortality. This raises questions about the validity of guidelines suggesting that the systolic blood pressure target should be in the range 130 to 135 mmHg.

Clinical guide:

The optimal blood pressure target for people with diabetes is unclear. However, existing trials suggest that treatment to a goal of <140 mmHg systolic and 80 mmHg diastolic is generally more effective than less intensive treatment. There is at present no evidence from clinical trials that more aggressive blood pressure goals (e.g., <130 mmHg or <120 mmHg) are beneficial.

Substantive changes

More intensive (lower) blood pressure targets versus less intensive (higher) blood pressure targets New evidence added. Categorisation changed (likely to be beneficial).

Articles from BMJ Clinical Evidence are provided here courtesy of BMJ Publishing Group

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