Angioplasty versus stenting for iliac artery lesions

Abstract

Background

Atherosclerosis of the iliac artery may result in a stenosis or occlusion, which is defined as iliac artery occlusive disease. A range of surgical and endovascular treatment options are available. Open surgical procedures have excellent patency rates but at the cost of substantial morbidity and mortality. Endovascular treatment has good safety and short‐term efficacy with decreased morbidity, complications and costs compared with open surgical procedures. Both percutaneous transluminal angioplasty (PTA) and stenting are commonly used endovascular treatment options for iliac artery occlusive disease. A stenotic or occlusive lesion of the iliac artery can be treated successfully by PTA alone. If PTA alone is technically unsuccessful, additional stent placement is indicated. Alternatively, a stent could be placed primarily to treat an iliac artery stenosis or occlusion (primary stenting, PS). However, there is limited evidence to prove which endovascular treatment strategy is superior for stenotic and occlusive lesions of the iliac arteries. This is an update of the review first published in 2015.

Objectives

To assess the effects of percutaneous transluminal angioplasty versus primary stenting for stenotic and occlusive lesions of the iliac artery.

Search methods

The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 24 September 2019. We also undertook reference checking and citation searching to identify additional studies.

Selection criteria

We included all randomised controlled trials (RCTs) comparing percutaneous transluminal angioplasty and primary stenting for iliac artery occlusive disease. We excluded quasi‐randomised trials, case reports, case‐control or cohort studies. We did not exclude studies based on the language of publication.

Data collection and analysis

Two authors independently selected suitable trials, extracted data, assessed trial quality and performed data analyses. When there was disagreement, consensus would be reached first by discussion between the two authors and, if needed, through consultation with a third author. We used GRADE criteria to assess the certainty of the evidence and presented the main results in a 'Summary of findings' table. The main outcomes of interest were technical success, complications, symptomatic improvement of peripheral arterial disease (PAD), patency, reinterventions, resolutions of symptoms and signs, and improvement in walking distance as reported by the patient.

Main results

We identified no new studies for this update. Previously, we identified two RCTs, with a combined total of 397 participants, as meeting the selection criteria. One study included mostly stenotic lesions (95%), whereas the second study included only iliac artery occlusions. Heterogeneity between these two studies meant it was not possible to pool the data. Both studies were of moderate methodological quality with some risk of bias relating to selective reporting and non‐blinding of participants and personnel. Both studies occurred in the 1990s and techniques have since evolved. We assessed the overall certainty of the evidence to be low. We downgraded by two levels: one for risk of bias concerns and one for imprecision and indirectness.

There was no evidence of a difference following percutaneous transluminal angioplasty (PTA) with selective stenting compared to primary stenting (PS) in technical success rates in either the study involving stenotic lesions (odds ratio (OR) 1.51, 95% confidence interval (CI) 0.77 to 2.99; 279 participants; low certainty evidence); or the study involving iliac artery occlusions (OR 2.95, 95% CI 0.12 to 73.90; 112 participants; low certainty evidence). In one trial, PTA of iliac artery occlusions resulted in a higher rate of major complications, especially distal embolisation (OR 4.50 95% CI 1.18 to 17.14; 1 study, 112 participants; low certainty evidence). Immediate complications were similar in the second study (OR 1.81, 95% CI 0.64 to 5.13; 1 study, 279 participants; low certainty evidence). Neither study reported on delayed complications. No evidence of a difference was seen in symptomatic improvement (OR 1.03, 95% CI 0.47 to 2.27; 1 study, 157 participants; low certainty evidence). The second study did not provide data but reported no differences. For the outcome of patency, no evidence of a difference was seen in the study involving iliac occlusion at two years (OR 1.60, 95% CI 0.34 to 7.44; 1 study, 57 participants; low certainty evidence); or the study involving stenotic lesions at two years (71.3% in the PS group versus 69.9% in the PTA group). Only one study reported on reintervention (six to eight years, OR 1.22, 95% CI 0.67 to 2.23; 1 study, 279 participants; low certainty evidence); and resolution of symptoms and signs (12 months, OR 1.14, 95% CI 0.65 to 2.00; 1 study, 219 participants; low certainty evidence), with no evidence of a difference detected in either outcome. Neither study reported on improvement in walking distance as reported by the patient.

Authors' conclusions

There is insufficient evidence to make general conclusions about the effects of percutaneous transluminal angioplasty versus primary stenting for stenotic and occlusive lesions of the iliac artery. Data from one study indicate that primary stenting in iliac artery occlusions may result in lower distal embolisation rates (low certainty evidence). The evidence in this review, based on two studies, was assessed as low certainty, with downgrading decisions based on limitations in risk of bias, imprecision and indirectness. More studies are required to strengthen our confidence in the results.

Plain language summary

Effectiveness of angioplasty compared with stenting in atherosclerotic disease of the iliac arteries

Background

Atherosclerosis in the iliac artery (main pelvic artery towards the leg) may result in narrowing or obstruction (occlusion), leading to reduced blood flow to the leg. This is called iliac artery occlusive disease. Iliac artery occlusive disease may lead to symptoms of pain in the legs when walking (intermittent claudication), pain at rest, or ulcers of the foot or leg. A range of surgical and endovascular (from inside the artery, e.g. angioplasty) treatment options are available. Open surgical procedures have excellent patency rates (percentage of the vessels that remain open) but at the cost of substantial illness and death. Endovascular treatment has good safety and short‐term effectiveness with decreased illness, complications and costs compared with open surgical procedures. Percutaneous transluminal angioplasty (PTA; dilation of the artery with a balloon) and stenting (insertion of a small mesh tube) are widely used endovascular treatment options for iliac artery occlusive disease. A narrowing or obstruction of the iliac artery can be treated successfully by PTA alone. If PTA alone is not successful, an additional stent can be placed. Alternatively, a stent could be placed on its own to treat an iliac narrowing or obstruction (this is called primary stenting (PS)). However, there is limited evidence to prove which endovascular treatment strategy is better for lesions that restrict the iliac arteries. This review investigates whether it is better to place a stent in the first instance, or only under particular circumstances.

Study characteristics and key results

We found no new studies for this update. Previously, we had identified two studies with a combined total of 397 participants relevant to this topic. Combining the data was not possible due to the differences between the two included studies. The evidence in this Cochrane Review is current to 24 September 2019.

For the following outcomes of interest, no clear differences emerged between the two types of treatment: technical success of the procedure, improvement in the severity of the arterial occlusive disease, or patency of the treated vessel. However, in one study, which only included iliac artery occlusions, fewer complications were observed in the group of participants treated with PS. Neither study reported on delayed complications. One study reported on reintervention, and resolution of symptoms and signs, with no evidence of a difference detected between the PS group and the PTA group. Neither study reported on improvement in walking distance. More research on this subject is necessary.

Reliability of the evidence

Both studies had some risk of bias relating to selective reporting and non‐blinding of participants and personnel. Both studies occurred in the 1990s and techniques have since evolved. We considered the overall certainty of the evidence to be low due to this risk of bias, the small number of included studies and the differences in the types of patients that were included.

Summary of findings

Summary of findings 1. Angioplasty compared to primary stenting for iliac artery stenotic lesions.

Percutaneous transluminal angioplasty (PTA) compared to primary stenting (PS) for iliac artery stenotic lesions
Patient or population: patients with symptomatic Iliac artery lesions Setting: hospital Intervention: PTA with selective stenting Comparison: PS
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with PS	Risk with PTA with selective stenting
Technical success (immediate)	See comment			391 (2 RCTs)	⊕⊕⊝⊝a low	Both trials reported on technical success but due to clinical heterogeneity (types of lesions included and outcome definitions) we were unable to pool data. Dutch Iliac Stent Trial included mostly stenoses and no evidence of a difference between the PTA and PS groups was seen (OR 1.51, 95% CI 0.77 to 2.99). Analysis of data from the STAG trial indicated no evidence of a difference between the groups (OR 2.95, 95% CI 0.12 to 73.90).
Incidence of complications (immediate)	See comment			391 (2 RCTs)	⊕⊕⊝⊝a low	Both trials reported on complications but due to clinical heterogeneity (types of lesions included and outcome definitions) we were unable to pool data. In Dutch Iliac Stent Trial, including mostly stenoses, there was no evidence of a difference in complications between the groups (OR 1.81, 95% CI 0.64 to 5.13). In the STAG trial, which included only occlusions, complications occurred more often in the PTA group (OR 4.50, 95% CI 1.18 to 17.14). 9/11 major complications were episodes of distal embolisation in the PTA group compared to 2 in the PS group, which resulted in the study being stopped prematurely.
Improvement in the stage of PAD according to Rutherford's criteria (one year)	800 per 1000	805 per 1000 (653 to 901)	OR 1.03 (0.47 to 2.27)	157 (1 RCT)	⊕⊕⊝⊝b low	‐
Primary patency (two years)	833 per 1000	889 per 1000 (630 to 974)	OR 1.60 (0.34 to 7.44)	57 (1 RCT)	⊕⊕⊝⊝c low	‐
Reinterventions (six to eight years)	175 per 1000	205 per 1000 (124 to 321)	OR 1.22 (0.67 to 2.23)	279 (1 RCT)	⊕⊕⊝⊝b low	‐
Resolution of symptoms and signs (one year)	643 per 1000	672 per 1000 (539 to 783)	OR 1.14 (0.65 to 2.00)	219 (1 RCT)	⊕⊕⊝⊝b low	‐
Improvement in walking distance as reported by the patient	‐			‐	‐	None of the included trials reported on improvement in walking distance
*The risk in the intervention group (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). CI: confidence interval; OR: odds ratio; PS: primary stenting; PTA: percutaneous transluminal angioplasty; RCT: randomised controlled trial
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low‐certainty: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

^aWe downgraded by one level due to risk of bias concerns (no blinding, high risk of reporting bias (Dutch Iliac Stent Trial), high risk of attrition bias (STAG trial) and another one level for imprecision (few participants and events) and indirectness (participants were included in the 1990s, endovascular techniques and materials have since evolved considerably)

^bWe downgraded by one level due to risk of bias concerns (no blinding, high risk of reporting bias) and another one level for imprecision (few participants and events) and indirectness (participants were included in the 1990s, endovascular techniques and materials have since evolved considerably)

^c We downgraded by one level due to risk of bias concerns (no blinding, high risk of attrition bias) and another one level for imprecision (few participants and events) and indirectness (participants were included in the 1990s, endovascular techniques and materials have since evolved considerably)

Background

Peripheral artery disease (PAD) involving the lower limbs is a manifestation of systemic atherosclerosis and can occur in up to 3% to 10% of the general population. The prevalence is higher with older age, affecting up to 15% to 20% of people aged over 70 years (Selvin 2004). In up to 30% of patients with PAD, the iliac artery is involved. PAD may lead to intermittent claudication, or in cases of more advanced disease, critical limb ischaemia (CLI). In the past, open bypass surgery was the therapy of choice. In recent years, endovascular treatment has gained popularity and has been shown to be safe and effective even in advanced lesions (Gandini 2007; Jongkind 2010).

Description of the condition

Atherosclerosis commonly affects the distal aorta and the iliac arteries. Although most patients are asymptomatic, an arterial stenosis or occlusion may result in symptoms, depending on the extent of involvement and the availability of collaterals (Weitz 1996). Restriction of blood flow initially leads to intermittent claudication. Further reduction in blood may result in ischaemic rest pain, ulceration, tissue loss and gangrene (Rutherford 1997). Treatment of this impaired vascularisation is important since PAD significantly impairs quality of life and can result in amputation of the affected limb (Norgren 2007).

Description of the intervention

A range of surgical and endovascular options are available for the treatment of stenotic and occlusive lesions in the iliac arteries. Open surgical procedures have excellent patency rates (intermittent claudication: 85% to 92%; CLI: 78% to 83%), at the cost of substantial morbidity and mortality (de Vries 1997). Endovascular treatment has good safety and short‐term efficacy with decreased mortality, morbidity and hospital stay compared with open surgical procedures (Jongkind 2010). Endovascular interventions can be repeated if the lesion recurs during follow‐up (Mousa 2007).

How the intervention might work

Both percutaneous transluminal angioplasty (PTA) and stenting are widely used endovascular treatment options for iliac artery occlusive disease. A stenotic or occlusive lesion of the iliac artery can be treated successfully by PTA alone. If PTA alone is not successful, additional stent placement is indicated. Lack of success may be defined as either a suboptimal angiographic result without improvement of blood pressure gradient, or no clinical improvement. Alternatively, a stent could be placed primarily to treat an iliac artery stenosis or occlusion. The rationale for stent placement would be to prevent elastic recoil of the stenosis after angioplasty and thus reduce restenosis rates. On the other hand, the stent may cause the local vasculature to react with an inflammatory response that precipitates neointimal proliferation and tissue ingrowth and thus leads to in‐stent restenosis (Hoffmann 1996).

Why it is important to do this review

Endovascular treatment of iliac artery occlusive disease is considered safe and effective (Jongkind 2010), and is currently the most commonly used treatment for this indication. Both selective stent placement as a bail‐out treatment for unsatisfactory results of PTA and primary stenting (PS) of iliac artery occlusive disease are advocated (Bosch 1997). However, there is limited evidence to prove which endovascular treatment strategy is superior for stenotic and occlusive lesions of the iliac arteries.

One meta‐analysis, based on non‐randomised trials, showed higher technical success and patency rates after PS (Bosch 1997). However, a large RCT, the Dutch Iliac Stent Trial, initiated by the same study group, has shown better symptomatic success with PTA and selective stent placement compared with PS placement, although both PTA and PS groups showed similar rates of iliac artery patency, ankle brachial index (ABI) and quality of life (Klein 2006). A large observational series has reported that more than 70% of iliac artery lesions could be treated successfully with PTA alone (Kudo 2005), thus without costly stenting. Although guidelines on treatment of iliac artery occlusive disease are available, they do not recommend a specific treatment (Tsetis 2008). As a result, the approach to treatment of iliac artery lesions varies widely between centres. This is an update of the review first published in 2015 (Bekken 2015).

Objectives

To assess the effects of percutaneous transluminal angioplasty versus primary stenting for stenotic and occlusive lesions of the iliac artery.

Methods

Criteria for considering studies for this review

Types of studies

We included all randomised controlled trials (RCTs) comparing percutaneous transluminal angioplasty (PTA) and primary stenting (PS) for iliac artery stenoses and occlusions. We considered trials in which balloons or drug‐eluting balloons were compared with stents or drug‐eluting stents or covered stents for iliac artery stenoses and occlusions for inclusion. We also considered multi‐armed RCTs if they compared between these two interventions. We did not include quasi‐randomised trials, case reports, case‐control or cohort studies. We did not exclude studies based on the language of publication. Trials assessing angioplasty versus primary stenting for superficial femoral artery lesions and infrapopliteal arterial lesions are reviewed in separate Cochrane reviews (Chowdhury 2014; Hsu 2018).

Types of participants

We included participants with symptomatic iliac artery occlusive disease. There were no restrictions based on either gender or age.

Types of interventions

• Percutaneous transluminal angioplasty (PTA), with or without selective stent placement

• Primary stenting (PS)

Types of outcome measures

Primary outcomes

• Technical success of the procedure (ability to restore more than 50% of the lumen)

• Incidence of complications:

  • Immediate (< 72 hours): e.g. dissection, thrombosis, infection, distal embolisation

  • Delayed (> 72 hours): e.g. worsening of disease, pseudoaneurysm formation

• Symptomatic improvement: improvement in the stage of PAD according to Rutherford's criteria (Rutherford 1997)

• Patency of the treated vessel as assessed by duplex sonography, computed tomography angiography (CTA), magnetic resonance angiography (MRA) or digital subtraction angiography (DSA)

Secondary outcomes

• Reintervention of the treated lesion

• Resolution of symptoms and signs

• Improvement in walking distance as reported by the patient

• Improvement of quality of life

• Measured claudication distance

• Ankle brachial index (ABI)

• Ulcer healing

• Major amputation‐free survival (survival without above‐ankle amputation)

Search methods for identification of studies

Electronic searches

For this update, the Cochrane Vascular Information Specialist conducted systematic searches of the following databases for randomised controlled trials and controlled clinical trials without language, publication year or publication status restrictions.

• The Cochrane Vascular Specialised Register via the Cochrane Register of Studies (CRS‐Web searched on 24 September 2019).

• The Cochrane Central Register of Controlled Trials (CENTRAL) Cochrane Register of Studies Online (CRSO 2019, 8).

• MEDLINE (Ovid MEDLINE® Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE® Daily and Ovid MEDLINE®) (searched from 01 January 2017 to 24 September 2019).

• Embase Ovid (searched from 01 January 2017 to 24 September 2019).

• CINAHL EBSCO (searched from 01 January 2017 to 24 September 2019).

• AMED Ovid (searched from 01 January 2017 to 24 September 2019).

The Information Specialist modelled search strategies for other databases on the search strategy designed for CENTRAL. Where appropriate, they were combined with adaptations of the highly sensitive search strategy designed by the Cochrane Collaboration for identifying randomised controlled trials and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Chapter 6, Lefebvre 2011). Search strategies for major databases are provided in Appendix 1.

The Information Specialist searched the following trials registries on 24 September 2019.

• The World Health Organization International Clinical Trials Registry Platform (who.int/trialsearch).

• ClinicalTrials.gov (clinicaltrials.gov).

Searching other resources

We searched references and bibliographies of relevant papers for additional references.

Data collection and analysis

Selection of studies

Two review authors (JB and NA) independently carried out selection of studies for inclusion. A third author (BF) resolved disagreements.

Data extraction and management

We identified no new studies for this update. In the previous version, two review authors (JB and HJ) extracted, assessed and coded data independently using the data collection form provided by Cochrane Vascular, adapted specifically for the review. Another review author (BF) resolved disagreements. One review author (JB) entered data into RevMan 5.3 (RevMan 2014), and a second review author (HJ) cross‐checked the data. Statistical analysis followed the standard methods of Cochrane Vascular. We performed all analyses using RevMan 5.3.

Assessment of risk of bias in included studies

In the previous version, two review authors (JB and HJ) independently used Cochrane's 'risk of bias' tool for assessing risk of bias for the included studies (Higgins 2011). This tool provides a protocol for judgements in these bias domains: sequence generation; allocation methods; blinding; incomplete outcome data; selective outcome reporting; and any other relevant biases. We judged the domains to be at high, low or unclear risk of bias. We resolved any disagreements by discussion with a third review author (BF). If necessary, we contacted the authors of the trials for clarification.

Measures of treatment effect

For dichotomous outcomes, we intended to calculate the relative risk (risk ratio (RR) or risk difference (RD)), to measure any treatment effect. However, as data were sparse, we used odds ratio (OR) only. For continuous outcomes, we intended to use the mean difference (MD) or standardised mean difference (SMD) if data were available.

Unit of analysis issues

We considered each individual participant as the unit of analysis. The Dutch Iliac Stent Trial reported reintervention rate at five years per segment instead of per individual participant, and therefore data are reported as such.

Dealing with missing data

In the previous version, we contacted the authors of the respective trials directly by email or fax, to ask for missing data. If studies had a dropout rate of more than 20%, we considered them of low quality and excluded them from the meta‐analysis. In addition, we performed a sensitivity analysis.

Assessment of heterogeneity

We constructed a forest plot to display the results and to examine possible heterogeneity between the studies. In addition to the Chi² test, we used the I² statistic to measure the level of heterogeneity.

Assessment of reporting biases

We planned to construct a funnel plot to assess publication bias if sufficient studies (> 10) were available for meta‐analysis (Higgins 2011).

Data synthesis

We planned to summarise the data using either the fixed‐effect or the random‐effects model. If heterogeneity was present (I² > 50%), we used the random‐effects model method. If not, we used a fixed‐effect model.

Subgroup analysis and investigation of heterogeneity

We planned to conduct the following subgroup analyses, if sufficient data were available.

• Moderate versus severe disease (Rutherford 1997).

• Length of the stenotic segment: short (≤ 3 cm) versus long (3 cm to 10 cm) (Norgren 2007).

• According to the Trans‐Atlantic Inter‐Society Consensus on Management of Peripheral Arterial Disease (TASC) classification of aorto‐iliac lesions (Norgren 2007).

• Stenosis versus occlusion.

• Location of stenosis:

  • involving the common iliac artery alone versus external iliac artery alone versus both arteries;

  • distance from the aortic bifurcation (< 1 cm versus > 1 cm);

  • distance from the hip joint (< 1 cm versus > 1 cm).

• Usage of the intraluminal versus subintimal space for endovascular treatment.

• Self‐expandable stent versus balloon‐mounted stent.

• Whether balloon angioplasty was done either before stenting or after stenting.

Sensitivity analysis

We planned to perform sensitivity analyses by excluding:

• randomised controlled trials of low methodological quality;

• industry‐funded studies.

Summary of findings and assessment of the certainty of the evidence

For this update we used GRADEpro software (GRADEpro GDT 2015), to prepare a 'Summary of findings' table describing the key information presented in the review, comparing angioplasty versus stenting for iliac artery lesions in patients with symptomatic Iliac artery occlusive disease. We reported on the following outcomes: technical success; immediate complications; symptomatic improvement; primary patency; reinterventions; resolutions of symptoms and signs; and improvement in walking distance as reported by the patient; as described in the Types of outcome measures. We based this table on the methods described in Chapters 11 and 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We evaluated the certainty of the evidence for each outcome as high, moderate, low, or very low, using the GRADE approach. We based these evaluations on the following criteria: risk of bias; inconsistency; indirectness; imprecision; and publication bias (Atkins 2004; Guyatt 2008).

Results

Description of studies

Results of the search

For this update, we did not identify any new included studies. We excluded nine new studies. See Figure 1.

1.

Study flow diagram.

Included studies

We identified no new studies for this update. See Characteristics of included studies for details of the included studies. To date, we have identified two RCTs (11 publications) in the literature comparing the results of angioplasty and stenting in iliac artery occlusive disease.

We evaluated the full text of the 11 articles identified for inclusion and categorised them into two groups:

• The first group was the Dutch Iliac Stent Trial (DIST), which consisted of eight publications. Three articles provided information on short‐term and long‐term results of percutaneous transluminal angioplasty (PTA) versus primary stenting (PS) (Klein 2004; Klein 2006; Tetteroo 1998). The other articles were about cost‐effectiveness, comparisons of intra‐arterial pressure gradients and haemodynamic criteria after stent placement.

• The second group consisted of two congress abstracts and one full publication concerning the STAG trial. We only used data from the full publication in this review.

The Dutch Iliac Stent Trial was performed from 1993 until 1997, and has published its early, mid‐term and late results in 1998, 2004 and 2006. The second study is the STAG trial, which was performed from 1995 until 2002, and published its two‐year follow‐up in 2013.

Excluded studies

For this update, we assessed nine new studies as excluded (Bolt 2019; Choi 2016; Deloose 2017; Hunt 2017; Krankenberg 2017; NCT02209350; NCT03315884; NCT03414515; NCT04023370), bringing the total to fourteen excluded studies (Bekken 2012; Bolt 2019; Choi 2016; Dake 2007; Deloose 2017; Hunt 2017; Katzen 2006; Kauffmann 1991a; Krankenberg 2017; Mwipatayi 2011; NCT02209350; NCT03315884; NCT03414515; NCT04023370). See Characteristics of excluded studies for details of the excluded studies.

Three studies concerned the femoropopliteal arteries rather than the iliac arteries (Dake 2007; Hunt 2017; Katzen 2006). Two studies were RCTs comparing bare‐metal and covered stents in the iliac artery, not PTA with PS (Bekken 2012; Mwipatayi 2011). Six studies compared other endovascular interventions of the iliac artery, not PTA with PS (Bolt 2019; Choi 2016; Krankenberg 2017; NCT02209350; NCT03315884; NCT04023370). Two studies were prospective, non‐randomised case series of PTA and PS (Deloose 2017; NCT03414515). Some of these are protocols or entries in trial registries, without published results. 

We found one quasi‐randomised controlled trial comparing PTA with PS (Kauffmann 1991a). The publications of this study consisted of multiple conference abstracts, most of them published while the study was in progress. The most recent conference abstract consisted of 247 participants (Richter 1993). However, the only full publication was at an earlier stage when the study had recruited 131 patients (Kauffmann 1991b). The full text of this article was in the German language. JB translated this article before we made the final decision to exclude the study.

Risk of bias in included studies

See also Characteristics of included studies, Figure 2 and Figure 3.

2.

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

3.

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

Allocation

We judged both included studies, Dutch Iliac Stent Trial and STAG trial, to be of low risk for selection bias, as both studies used random sequence generation and adequate allocation concealment.

Blinding

We judged both included studies to be of high risk for blinding of participants and personnel (Dutch Iliac Stent Trial; STAG trial). We judged the risk for blinding of outcome assessment as unclear for both studies as details of blinding were insufficient or lacking.

Incomplete outcome data

We assessed the Dutch Iliac Stent Trial as low risk for incomplete outcome data, as six to eight‐year results were reported on a substantial number of participants. We assessed the STAG trial as high risk, as only a limited number of participants completed full follow‐up and no explanation for this was given.

Selective reporting

The study protocol was not published for either the Dutch Iliac Stent Trial or the STAG trial. Therefore we assessed the risk as unclear for the STAG trial. However, the final publication of the Dutch Iliac Stent Trial used different outcome measures than in their previous publications, and the outcomes that were reported were different from how they were defined in the methods section of the article (see paragraphs on 'Symptomatic improvement: Improvement in the stage of PAD' and 'resolution of symptoms and signs'). Therefore, we assessed this as a high risk of bias.

Other potential sources of bias

Government‐provided grants funded both studies. Cordis, the company that manufactures Palmaz stents, funded the long‐term follow‐up from the Dutch Iliac Stent Trial. However, it is stated that the investigators were in full control of the data. Therefore, we scored both trials as low risk of bias in this domain. We did not identify any other potential sources of bias; therefore, we scored both trials as low risk of bias in this domain.

Effects of interventions

See: Table 1

Pooling of data, planned subgroup analysis, sensitivity analysis and creation of funnel plots were not possible, due to the fact that only two studies were included and the studies were heterogeneous. The Dutch Iliac Stent Trial included mostly stenotic lesions (95%), while the STAG trial included occlusive lesions only. In addition, the definitions of the various outcomes reported in both studies were not comparable.

Technical success of the procedure

In the Dutch Iliac Stent Trial, the treatment was considered a technical success when the pressure gradient across the treated segment was equal to or less than 10 mmHg after the procedure and during pharmacologically‐induced vasodilatation. Study authors reported that technical success was equal in both groups, with 120 of 136 (88%) of patients in the PTA group achieving technical success, compared to 119 of 143 (84%) of patients in the PS group (OR 1.51, 95% confidence interval (CI) 0.77 to 2.99; 1 study, 279 participants; low‐certainty evidence; Analysis 1.1).

1.1. Analysis.

Comparison 1: Angioplasty versus primary stenting for iliac artery stenotic lesions., Outcome 1: Technical success

The STAG trial defined technical success as the presence of antegrade flow through the treated segment. Therefore, patients in the PTA group who required a stent were categorised as having a technical failure. In the PTA group, 46 of 55 (84%) patients had a technical success, versus 56 of 57 (98%) in the PS group, which was reported by the study authors as a statistically significant difference (reported P value = 0.007). However, in the PTA group, all nine patients without flow were treated successfully by secondary stenting. The review authors believe it would be more feasible to consider these patients a technical success, since secondary stenting was part of the treatment strategy. In that case, technical success in the PTA group would be 100% with no clear difference between both groups (OR 2.95, 95% CI 0.12 to 73.90; 1 study, 112 participants; low‐certainty evidence; Analysis 1.1).

Incidence of complications

Immediate complications (< 72 hours)

Both the Dutch Iliac Stent Trial and the STAG trial reported on early or immediate complications.

In the Dutch Iliac Stent Trial, authors did not state in their publications’ methods sections how complications were defined. They made no distinction between major or minor complications. They stated that complications included haematoma at the puncture site, arterial‐wall perforation, acute occlusion of the treated arterial segment, embolism and vasovagal collapse. They did not report how these complications were distributed over both treatment groups. Complications occurred in 7% (10/136) of patients in the PTA group and in 4% (6/143) of patients in the PS group (OR 1.81, 95% CI 0.64 to 5.13; 1 study, 279 participants; low‐certainty evidence; Analysis 1.2). Surgical intervention was necessary in two patients in the PTA group; however, it is not reported for what indication. Stent occlusion as indicated by arterial thrombosis did not occur.

1.2. Analysis.

Comparison 1: Angioplasty versus primary stenting for iliac artery stenotic lesions., Outcome 2: Incidence of complications

In the STAG trial, investigators defined major complications as those resulting in death, permanent disability, unplanned amputation due to the intervention, an unexpected or unplanned secondary procedure (excluding secondary stent placement), delayed hospital discharge or blood transfusion. These occurred more often in the PTA group (20%, 11/55), compared to the PS group (5%, 3/57) (OR 4.50, 95% CI 1.18 to 17.14; 1 study, 112 participants; low‐certainty evidence; Analysis 1.2). Nine of 11 major complications in the PTA group, and two of three in the PS group, were episodes of distal embolisation. For this reason, investigators stopped the study prematurely. The other complications were two acute thromboses in the PTA group, and one arterial wall rupture in the PS group.

Delayed complications (> 72 hours)

Neither of the included trials reported delayed complications (Dutch Iliac Stent Trial; STAG trial).

Symptomatic improvement: improvement in the stage of PAD according to Rutherford's criteria

The full publication from the STAG trial does not report on improvement in the stage of peripheral arterial disease (PAD). In the two abstracts from congress presentations, authors state that "clinical outcome was assessed using the Rutherford scale at 1 month, 6 months, 1 year and 2 years" and that "there were no differences in clinical outcomes at 2 years" (Goode 2010; Goode 2011). However, authors reported no data to support these statements.

The Dutch Iliac Stent Trial reported on improvement in the stage of PAD, termed clinical success, at three months, one year, two years and six to eight years of follow‐up. For the first three time points, clinical success was defined as improvement of at least one clinical (Rutherford) category compared with the pre‐treatment assessment. At three months, one year and two years, the study authors observed no difference between both treatment strategies. At three months, clinical success was obtained in 82% (101/123) of patients in the percutaneous transluminal angioplasty (PTA) group compared to 76% (103/135) of patients in the primary stent (PS) group (OR 1.43, 95% CI 0.78 to 2.62; 1 study, 258 participants; Analysis 1.3). At one year, clinical success was obtained in 81% (62/77) of patients in the PTA group compared to 80% (64/80) of patients in the primary stent group (OR 1.03, 95% CI 0.47 to 2.27; 1 study, 157 participants; low‐certainty evidence; Analysis 1.3). At two years, clinical success was obtained in 77% (26/34) of patients in the PTA group compared to 78% (29/37) of patients in the PS group (OR 0.90, 95% CI 0.29 to 2.73; 1 study, 71 participants; Analysis 1.3).

1.3. Analysis.

Comparison 1: Angioplasty versus primary stenting for iliac artery stenotic lesions., Outcome 3: Symptomatic improvement

For the six to eight‐year time point, the methods section of the article states that symptomatic success was defined as an increase of at least one Fontaine stage. However, the article only reports the current Fontaine stage, and not the proportion of patients that had an increase in Fontaine stage. This is not symptomatic improvement as defined in the methods section of the trial or of this review, and should actually be classified as 'resolution of signs and symptoms'. Therefore, we report these results below in the appropriate section of this review. The article does not report the actual improvement in the stage of PAD rate at this time point. We contacted the study authors but received no response.

Patency of the treated vessel

Both the Dutch Iliac Stent Trial and the STAG trial reported on patency rates.

In the STAG trial, study authors defined patency as any flow through the treated segment measured by angiography after one and two years. They defined primary patency as patency without any reintervention, and secondary patency as patency after any successful reintervention. Study authors found no evidence of a difference at either time point. Primary patency at one year was 95% in both groups (PTA 40/42, PS 39/41; OR 1.03, 95% CI 0.14 to 7.65; 1 study, 83 participants; Analysis 1.4). At two years, primary patency was 89% (24/27) in the PTA group versus 83% (25/30) in the PS group (OR 1.60, 95% CI 0.34 to 7.44; 1 study, 57 participants; low‐certainty evidence; Analysis 1.4). Study authors did not report secondary patency rates, but did state that there was no significant difference.

1.4. Analysis.

Comparison 1: Angioplasty versus primary stenting for iliac artery stenotic lesions., Outcome 4: Primary patency

In the Dutch Iliac Stent Trial, investigators assessed patency by duplex ultrasonography. They deemed the iliac artery patent when the peak systolic velocity ratio was less than 2.5. The study authors reported patency as a life table analysis in two different publications of this study: primary patency at two years follow‐up in one, and secondary patency for up to six to eight years follow‐up in the other. At two years, reported primary patency rates were 71.3% in the PS group versus 69.9% in the PTA group, with a reported P value of 0.2. It is not clear how many patients had reached the two‐year follow‐up at the time of publication. The secondary patency rates, which are reported at six to eight years, were similar, with 83% (90/109) in the PS group versus 74% (67/90) in the PTA group (OR 0.61, 95% CI 0.31 to 1.22; 1 study, 199 participants; Analysis 1.5).

1.5. Analysis.

Comparison 1: Angioplasty versus primary stenting for iliac artery stenotic lesions., Outcome 5: Secondary patency

Reintervention of the treated lesion

Only the Dutch Iliac Stent Trial reported reintervention rates, and no evidence of a difference was found at any time point in follow‐up. At two years, reintervention rates were 4% (6/136 patients) in the PTA group versus 7% (10/143 patients) in the PS group (OR 0.61, 95% CI 0.22 to 1.74; 1 study, 279 participants; Analysis 1.6). At five years, reinterventions were reported as treated segments ‐ not per patient. Reintervention rates were 20% (33/169 treated segments, PTA group) versus 18% (33/187 treated segments, PS group) (OR 1.13, 95% CI 0.66 to 1.93; 1 study, 356 treated segments; Analysis 1.6). Finally, at six to eight years, 17% of patients (25/143) in the PS group and 21% (28/136) in the PTA group had required reintervention (OR 1.22, 95% CI 0.67 to 2.23; 1 study, 279 participants; low‐certainty evidence; Analysis 1.6). Study authors stated that there was no difference in the number of endovascular and surgical reintervention procedures between the two treatment groups, but gave no numbers.

1.6. Analysis.

Comparison 1: Angioplasty versus primary stenting for iliac artery stenotic lesions., Outcome 6: Reinterventions

Resolution of symptoms and signs

The STAG trial did not report on this outcome.

The Dutch Iliac Stent Trial reported on resolution of symptoms and signs, defined as Fontaine stage 1, at three, 12 and 24 months, and six to eight years. The investigators reported on symptomatic improvement at six to eight years, but as noted above, we suggest that this should actually be termed as resolution of symptoms and signs. There was no evidence of a difference between the groups at any of the time points (3 months: OR 1.21, 95% CI 0.72 to 2.01; 1 study, 263 participants; 12 months: OR 1.14, 95% CI 0.65 to 2.00; 1 study, 219 participants; low‐certainty evidence; 24 months: OR 0.89, 95% CI 0.49 to 1.63; 1 study, 183 participants; six to eight years: OR 1.81, 95% CI 0.97 to 3.37; 1 study, 168 participants; Analysis 1.7). The study authors report that at the six‐ to eight‐year time point, there is a significant difference in the percentage of participants with resolution of symptoms and signs (Fontaine stage 1) in favour of the PTA group (31/90 versus 38/78, hazard ratio (HR) 0.8 (95% CI 0.6 to 1.0)); however, they give no P value. Statistical analysis, by the review authors based on the data provided, shows no clear difference between the groups (OR 1.81, 95% CI 0.97 to 3.37; Analysis 1.7).

1.7. Analysis.

Comparison 1: Angioplasty versus primary stenting for iliac artery stenotic lesions., Outcome 7: Resolution of symptoms and signs

Improvement in walking distance as reported by the patient

The included studies did not report on this outcome.

Improvement of quality of life

Only the Dutch Iliac Stent Trial reported on quality of life improvement. Quality of life was measured with the RAND 36‐Item Health Survey at one, three, 12 and 24 months and at five years. The RAND‐36 scores nine health dimensions: physical functioning, physical role functioning, emotional role functioning, social functioning, bodily pain, general health perception, mental health, vitality and health change. The study authors reported that all scores, except for general health perception, were markedly higher in both groups than they were before treatment. The study authors state that survival analysis showed no differences in scores between the two treatment groups over the whole follow‐up period.

Measured claudication distance

The included studies did not report on this outcome.

Ankle brachial index

Only the Dutch Iliac Stent Trial reported on ankle brachial index (ABI) values, at three months, 12 months, 24 months and six to eight years. At 24 months, the study authors reported a small difference between the two groups with a lower mean difference (MD) in ABI value in the PS group (MD 0.09, 95% CI 0.04 to 0.14; 1 study, 206 participants; Analysis 1.8), with an unclear clinical relevance. They found no evidence of a difference at the other time points.

1.8. Analysis.

Comparison 1: Angioplasty versus primary stenting for iliac artery stenotic lesions., Outcome 8: Ankle brachial index

Ulcer healing

The included studies did not report on this outcome.

Major amputation‐free survival

The included studies did not report on this outcome.

Discussion

Summary of main results

We did not identify any new studies for this update and we were unable to pool data from the two previously included studies due to clinical heterogeneity. There was no evidence of a difference in any of the primary outcomes of either study, except for immediate complications in one study.

Since additional stenting was considered a technical failure in the STAG trial, it reported a decreased technical success rate in the percutaneous transluminal angioplasty (PTA) group. The review authors believe additional stenting should not be considered a technical failure, as it is part of the treatment strategy. With this view, the technical success rates would be similar. In the Dutch Iliac Stent Trial, technical success rates in both groups were also comparable (low‐certainty evidence).

The STAG trial showed an increased major complication rate, especially distal embolism, in the PTA group compared to the PS group (20% versus 5%) (low‐certainty evidence). For this reason, the trial was stopped prematurely. The Dutch Iliac Stent Trial did not find any clear differences in complication rates (low‐certainty evidence). Unfortunately, the study authors did not report the distribution of specific complications, such as embolism, between groups.

For symptomatic improvement (improvement in the stage of PAD according to Rutherford's criteria), the study authors of the STAG trial reported "there were no differences in clinical outcomes at 2 years" without providing data. Data from the Dutch Iliac Stent Trial show no evidence of a difference in improvement in PAD stage between the groups at three months, one year (OR 1.03, 95% CI 0.47 to 2.27; 1 study, 157 participants; low‐certainty evidence); or two years. The Dutch Iliac Stent Trial reports significantly higher symptomatic success at six to eight years. However, the data presented by the trial authors actually reflect 'resolution of signs and symptoms', and based on the data provided, we find no evidence of a difference for this outcome at any time point.

Patency rates were comparable for both strategies, and were also comparable to patency rates reported in other studies (low‐certainty evidence).

The Dutch Iliac Stent Trial saw no evidence of a difference in reintervention rates between the groups.

The Dutch Iliac Stent Trial showed a higher mean ankle brachial index (ABI) at two years in the PTA group (1.0 versus 0.91; mean difference (MD) 0.09, 95% confidence interval (CI) 0.04 to 0.14; analysis performed by review authors). At other time points, no difference was detected. It is unlikely that the difference at two years is attributable to the study procedure and it may not be clinically relevant.

The Dutch Iliac Stent Trial showed an increased quality of life at three months, 12 months, 24 months and five years when compared to baseline, but no difference between the groups.

Neither of the included studies reported on improvement in walking distance, claudication distance, ulcer healing, major amputation‐free survival or incidence of delayed complications.

Overall completeness and applicability of evidence

The available evidence comes from only two studies, which were both performed in the 1990s. It is unclear whether ongoing improvements in stent design, and other innovations such as covered stents and drug‐eluting balloons and stents, which were not available at the time, would affect these results.

The STAG trial compared primary stent placement with PTA and selective stenting in case of no flow through the arterial segment, and included only occlusions. In 16% of patients in the PTA group, additional stent placement was performed. The Dutch Iliac Stent Trial also compared primary stent placement with PTA and selective stenting, however stenting was performed in case of a residual mean pressure gradient > 10 mmHg. This resulted in additional stent placement in 43% of patients in the PTA group. The Dutch Iliac Stent Trial included mainly stenotic lesions (95%). Thus, the two studies are heterogeneous and we deemed pooling of data inappropriate.

Of the 12 outcomes of interest, five were not assessed in either study: improvement in walking distance as reported by the patient, measured claudication distance, ulcer healing, major amputation‐free survival, and delayed complications. Only two outcomes were reported in both studies: technical success and patency of the treated vessel. The other outcomes were assessed in only one of the studies.

Quality of the evidence

The two studies that we included in this review did have some risk of bias, such as selective reporting and non‐blinding of participants and personnel. However, some bias is inevitable given the nature of the treatment. For example, blinding of personnel as to whether or not a stent is placed is not possible. Due to the heterogeneity among the studies, as discussed above, pooling was not possible. We selected seven outcomes (technical success; immediate complications; symptomatic improvement; primary patency; reinterventions; resolutions of symptoms and signs; and improvement in walking distance as reported by the patient) for presentation in a 'Summary of findings' table and assessed our certainty in the evidence using the GRADE criteria (see Table 1). We assessed the overall certainty of the evidence to be low. We downgraded by one level due to risk of bias concerns (no blinding, high risk of reporting bias (Dutch Iliac Stent Trial), high risk of attrition bias (STAG trial)) and another one level for imprecision (only two studies included, few participants and events), and indirectness (participants were included in the 1990s; endovascular techniques and materials have since evolved considerably).

Potential biases in the review process

We detected no biases in the review process. The Information Specialist performed a comprehensive search and we also performed a vigorous reference search. However, it is possible that unpublished studies or data may have been missed.

Agreements and disagreements with other studies or reviews

A meta‐analysis on the same topic, published almost 20 years ago, analysed cohort studies because no randomised controlled trials (RCTs) were available at the time (Bosch 1997). Bosch 1997 included a total of 2116 patients, and concluded that initial technical success was comparable in patients treated with PS and patients treated with PTA (96% versus 91%). Bosch 1997 also found that long‐term patency (four years) was significantly higher in the PS group. Based on their data, a relative risk reduction for loss of patency of 39% was calculated. Complication rate and mortality were not significantly different.

In our review, we did not show a difference in technical success, symptomatic improvement or patency. In the STAG trial, which included occlusions only, an increased number of major complications was found in the PTA group.

Authors' conclusions

Implications for practice.

There is insufficient evidence to make general conclusions about the effects of percutaneous transluminal angioplasty versus primary stenting for stenotic and occlusive lesions of the iliac artery. Data from one study indicated that primary stenting in iliac artery occlusions may result in lower distal embolisation rates (low‐certainty evidence). The evidence in this review, based on two studies, was assessed as low‐certainty evidence, with downgrading decisions based on limitations in risk of bias, imprecision and indirectness. More studies are required to strengthen our confidence in the results.

Implications for research.

More studies are required to strengthen our confidence in the results as the number of studies and total number of patients that could be included in this systematic review are small. Also, investigators initiated both studies in the 1990s. Since then, both stents and percutaneous transluminal angioplasty (PTA) balloons have seen many improvements, and new technologies ‐ such as covered stents and drug‐eluting balloons and stents ‐ have emerged. For example, in the Dutch Iliac Stent Trial, the stents were mounted on the balloons by hand, whereas nowadays all stents come premounted on balloons. It is unclear how these factors influence the results of our review. Based on our results, and on the fact that much has changed in endovascular techniques and materials since the publication of the studies included in this review, we would advise the initiation of new RCTs comparing primary stenting with PTA and selective stenting. Subgroup analyses should be performed for critical ischaemia versus claudication and for stenotic versus occlusive lesions.

What's new

Date	Event	Description
3 June 2020	New search has been performed	New search run. No new included studies identified, nine new studies were excluded.
3 June 2020	New citation required but conclusions have not changed	New search run. No new included studies identified, nine new studies were excluded. Text updated to reflect current Cochrane standards. 'Summary of findings' table added. No change to conclusions.

History

Protocol first published: Issue 1, 2009
Review first published: Issue 5, 2015

Appendices

Appendix 1. Database searches 2019

Source	Search strategy	Hits retrieved
CENTRAL	#1 MESH DESCRIPTOR Angioplasty EXPLODE ALL TREES 4338 #2 (angioplas* or percutan* or PTA or venoplasty):TI,AB,KY 22272 #3 (recanali* or revascular*):TI,AB,KY 12138 #4 dilat*:TI,AB,KY 11600 #5 (balloon or baloon):TI,AB,KY 9578 #6 MESH DESCRIPTOR Endovascular Procedures EXPLODE ALL TREES 7867 #7 endovascular:TI,AB,KY 3153 #8 MESH DESCRIPTOR Blood Vessel Prosthesis EXPLODE ALL TREES 438 #9 MESH DESCRIPTOR Blood Vessel Prosthesis Implantation EXPLODE ALL TREES 438 #10 MESH DESCRIPTOR Stents EXPLODE ALL TREES 3928 #11 (stent* or graft* or endograft* or endoprosthe*):TI,AB,KY 40672 #12 (powerlink or talent or excluder or aorfix or zenith or endologix or anaconda or Triascular or Cordis or Endurant or Quantum or Aneurx or Ancure or Advanta or Intracoil or Zilver or Luminex):TI,AB,KY 969 #13 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 75559 #14 MESH DESCRIPTOR Iliac Artery EXPLODE ALL TREES 160 #15 iliac:TI,AB,KY 1970 #16 #14 OR #15 1970 #17 #13 AND #16 877	426
Clinicaltrials.gov	Angioplasty OR Blood Vessel Prosthesis OR venoplasty OR balloon OR baloon OR Endovascular OR stent OR graft OR endograft OR endoprosthesis | Iliac	22
ICTRP Search Portal	Angioplasty OR Blood Vessel Prosthesis OR venoplasty OR balloon OR baloon OR Endovascular OR stent OR graft OR endograft OR endoprosthesis | Iliac	26
Medline (Ovid MEDLINE® Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE® Daily and Ovid MEDLINE®) 1946 to present (2017, 2018 and 2019 only)	1 exp Angioplasty/ 2 (angioplas* or percutan* or PTA or venoplasty).ti,ab. 3 (recanali* or revascular*).ti,ab. 4 dilat*.ti,ab. 5 (balloon or baloon).ti,ab. 6 exp Endovascular Procedures/ 7 endovascular.ti,ab. 8 exp Blood Vessel Prosthesis/ 9 exp Blood Vessel Prosthesis Implantation/ 10 exp Stents/ 11 (stent* or graft* or endograft* or endoprosthe*).ti,ab. 12 ().ti,ab. 13 or/1‐12 14 exp Iliac Artery/ 15 iliac.ti,ab. 16 14 or 15 17 13 and 16 18 randomized controlled trial.pt. 19 controlled clinical trial.pt. 20 randomized.ab. 21 placebo.ab. 22 drug therapy.fs. 23 randomly.ab. 24 trial.ab. 25 groups.ab. 26 or/18‐25 27 exp animals/ not humans.sh. 28 26 not 27 29 17 and 28	39
Embase 1974 to present (2017, 2018 and 2019 only)	1 exp angioplasty/ 2 (angioplas* or percutan* or PTA or venoplasty).ti,ab. 3 (recanali* or revascular*).ti,ab. 4 dilat*.ti,ab. 5 (balloon or baloon).ti,ab. 6 exp endovascular surgery/ 7 endovascular.ti,ab. 8 exp blood vessel prosthesis/ 9 exp blood vessel transplantation/ 10 exp stent/ 11 (stent* or graft* or endograft* or endoprosthe*).ti,ab. 12 (powerlink or talent or excluder or aorfix or zenith or endologix or anaconda or Triascular or Cordis or Endurant or Quantum or Aneurx or Ancure or Advanta or Intracoil or Zilver or Luminex).ti,ab. 13 or/1‐12 14 exp iliac artery/ 15 iliac.ti,ab. 16 14 or 15 17 13 and 16 18 randomized controlled trial/ 19 controlled clinical trial/ 20 random$.ti,ab. 21 randomization/ 22 intermethod comparison/ 23 placebo.ti,ab. 24 (compare or compared or comparison).ti. 25 ((evaluated or evaluate or evaluating or assessed or assess) and (compare or compared or comparing or comparison)).ab. 26 (open adj label).ti,ab. 27 ((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab. 28 double blind procedure/ 29 parallel group$1.ti,ab. 30 (crossover or cross over).ti,ab. 31 ((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab. 32 (assigned or allocated).ti,ab. 33 (controlled adj7 (study or design or trial)).ti,ab. 34 (volunteer or volunteers).ti,ab. 35 trial.ti. 36 or/18‐35 37 17 and 36	911
CINAHL (2017, 2018 and 2019 only)	S66 S50 AND S65 S65 S51 OR S52 OR S53 OR S54 OR S55 OR S56 OR S57 OR S58 OR S59 OR S60 OR S61 OR S62 OR S63 OR S64 S64 MH "Random Assignment" S63 MH "Triple‐Blind Studies" S62 MH "Double‐Blind Studies" S61 MH "Single‐Blind Studies" S60 MH "Crossover Design" S59 MH "Factorial Design" S58 MH "Placebos" S57 MH "Clinical Trials" S56 TX "multi‐centre study" OR "multi‐center study" OR "multicentre study" OR "multicenter study" OR "multi‐site study" S55 TX crossover OR "cross‐over" S54 AB placebo* S53 TX random* S52 TX trial* S51 TX "latin square" S50 S46 AND S49 S49 S47 OR S48 S48 TX iliac S47 (MH "Iliac Artery") S46 S35 OR S36 OR S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44 OR S45 S45 TX powerlink or talent or excluder or aorfix or zenith or endologix or anaconda or Triascular or Cordis or Endurant or Quantum or Aneurx or Ancure or Advanta or Intracoil or Zilver or Luminex S44 TX stent* or graft* or endograft* or endoprosthe* S43 (MH "Stents+") S42 (MH "Blood Vessel Prosthesis") S41 TX endovascular S40 (MH "Endovascular Procedures+") S39 TX balloon or baloon S38 TX dilat* S37 TX recanali* or revascular* S36 TX angioplas* or percutan* or PTA or venoplasty S35 (MH "Angioplasty+") S34 S32 AND S33 S33 EM 2017 OR EM 2018 OR 2019 EM S32 S16 AND S31 S31 S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 S30 MH "Random Assignment" S29 MH "Triple‐Blind Studies" S28 MH "Double‐Blind Studies" S27 MH "Single‐Blind Studies" S26 MH "Crossover Design" S25 MH "Factorial Design" S24 MH "Placebos" S23 MH "Clinical Trials" S22 TX "multi‐centre study" OR "multi‐center study" OR "multicentre study" OR "multicenter study" OR "multi‐site study" S21 TX crossover OR "cross‐over" S20 AB placebo* S19 TX random* S18 TX trial* S17 TX "latin square" S16 S12 AND S15 S15 S13 OR S14 S14 TX iliac S13 (MH "Iliac Artery") S12 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 S11 TX powerlink or talent or excluder or aorfix or zenith or endologix or anaconda or Triascular or Cordis or Endurant or Quantum or Aneurx or Ancure or Advanta or Intracoil or Zilver or Luminex S10 TX stent* or graft* or endograft* or endoprosthe* S9 (MH "Stents+") S8 (MH "Blood Vessel Prosthesis") S7 TX endovascular S6 (MH "Endovascular Procedures+") S5 TX balloon or baloon S4 TX dilat* S3 TX recanali* or revascular* S2 TX angioplas* or percutan* or PTA or venoplasty S1 (MH "Angioplasty+")	45
AMED (Allied and Complementary Medicine) 1985 onwards (2017, 2018 and 2019 only)	1 exp angioplasty/ 2 (angioplas* or percutan* or PTA or venoplasty).ti,ab. 3 (recanali* or revascular*).ti,ab. 4 dilat*.ti,ab. 5 (balloon or baloon).ti,ab. 6 endovascular.ti,ab. 7 exp blood vessel prosthesis/ 8 exp blood vessel transplantation/ 9 exp stent/ 10 (stent* or graft* or endograft* or endoprosthe*).ti,ab. 11 (powerlink or talent or excluder or aorfix or zenith or endologix or anaconda or Triascular or Cordis or Endurant or Quantum or Aneurx or Ancure or Advanta or Intracoil or Zilver or Luminex).ti,ab. 12 or/1‐11 13 exp Arteries/ 14 iliac.ti,ab. 15 13 or 14 16 12 and 15 17 exp CLINICAL TRIALS/ 18 RANDOM ALLOCATION/ 19 DOUBLE BLIND METHOD/ 20 Clinical trial.pt. 21 (clinic* adj trial*).tw. 22 ((singl* or doubl* or trebl* or tripl*) adj (blind* or mask*)).tw. 23 PLACEBOS/ 24 placebo*.tw. 25 random*.tw. 26 PROSPECTIVE STUDIES/ 27 or/17‐26 28 16 and 27	1

Data and analyses

Comparison 1. Angioplasty versus primary stenting for iliac artery stenotic lesions.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Technical success	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.2 Incidence of complications	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.2.1 Immediate complications	2		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.3 Symptomatic improvement	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.3.1 Three months	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.3.2 One year	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.3.3 Two years	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.4 Primary patency	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.4.1 One year	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.4.2 Two years	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.5 Secondary patency	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.5.1 Six to eight years	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.6 Reinterventions	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.6.1 Two years	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.6.2 Five years	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.6.3 Six to eight years	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.7 Resolution of symptoms and signs	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.7.1 Three months	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.7.2 One year	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.7.3 Two years	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.7.4 Six to eight years	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
1.8 Ankle brachial index	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.8.1 Three months	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.8.2 One year	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.8.3 Two years	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.8.4 Six to eight years	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Dutch Iliac Stent Trial.

Study characteristics
Methods	RCT comparing PS and primary PTA with selective stenting
Participants	This study was performed in the vascular surgery department of 6 large Dutch hospitals from November 1993 until March 1997. Inclusion criteria were IC, reduced ABI and stenosis < 10 cm or occlusion < 5 cm in CIA and/or EIA Exclusion criteria included occlusion not allowing passage of guidewire, stenosis involving distal aorta, severe comorbidity (e.g. severe cardiac or cerebrovascular abnormality, malignant disease), inability to understand Dutch, expected poor compliance and PTA or vascular surgery of the iliac artery < 12 months ago 365 potentially eligible patients were identified; 27 refused to participate; 59 excluded due to one or more criteria (lesions extending into distal aorta, no stenosis on angiography, stenosis > 10 cm, occlusions > 5 cm, mechanical passage of guidewire, PTA deemed insufficient) 279 patients were randomised (356 lesions); 143 (187 lesions) in PS, 136 (169 lesions) in PTA Sex: PS 73% male (102/143), PTA 73% male (37/136) Age: PS 59 (11), PTA 60 (10) Disease severity: Rutherford classification: PS I: 24% (35), II: 54% (77), III: 16% (23), IV: 5% (7), V: 1% (1) PTA I: 27% (37), II: 51% (69), III: 13% (18), IV: 8% (11), V: 1% (1) Co‐morbidities/risk factors: ‐ Tobacco use: PS 87% (124/143), PTA 94% (128/136) ‐ Diabetes: PS 9% (13/143), PTA 11% (15/136) ‐ Hypertension: PS 28% (40/143), PTA 27% (37/136) ‐ Cerebrovascular history: PS 14% (20/143), PTA 7% (9/136) ‐ Dyslipidaemia: PS 24% (34/143), PTA 26% (36/136) Location: CIA: PTA: 95 (69%); PS: 97 (70 %); EIA: PTA: 42 (31%); PS: 42 (30%)
Interventions	PS: a long 7‐F introducer sheath was placed across the targeted segment. The stent (Palmaz, Johnson & Johnson, Warren, NY, USA) was mounted by hand on a folded angioplasty balloon catheter. The stent‐balloon assembly was positioned at the site of the intended intervention, the sheath withdrawn and the stent deployed by inflation of the balloon. The stent diameter was determined by the width of the uninvolved portion of the vessel. PTA: "PTA was performed according to standard techniques". Secondary stenting was performed in cases in which the residual mean pressure gradient after PTA was greater than 10 mmHg. In 38% of lesions, stenting was required. All patients received anticoagulant medication in accordance with local guidelines or the individual preference of the physician who initially referred the patient for treatment.
Outcomes	Primary outcome: ‐ Clinical success ‐ improvement of at least one clinical category (short‐term results: Rutherford classification, long‐term results: Fontaine classification) (up to 6 to 8 years) Secondary outcomes: ‐ Patency of the treated vessel (up to 6 to 8 years) ‐ Initial technical success ‐ Procedural complications ‐ Cumulative patency as assessed by duplex ultrasonography (up to 6 to 8 years) ‐ Quality of life Failure in treating any one lesion was considered a failure in treating the patient.
Funding	Flanders Medical Research Program. The long‐term follow‐up was funded by Cordis.
Declarations of interest	No conflicts declared. It is stated that the investigators were in full control of the data for the long term follow up.
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"For each hospital, a separate computer‐generated randomisation table was produced to limit imbalance between treatment assignments to four."
Allocation concealment (selection bias)	Low risk	"This table was kept at the trial office and was not available to the treating physicians. The trial assignment was revealed …. by a trial co‐worker."
Blinding of participants and personnel (performance bias) All outcomes	High risk	"We decided that to conceal the assigned treatment from patients or physicians was not feasible."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	It is unclear if personnel performing ABI measurements, duplex and clinical examination were blinded. Complications and technical success are probably scored by the operating personnel so these were probably not blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Even for long‐term results there was a relatively low number of patients lost to follow‐up.
Selective reporting (reporting bias)	High risk	Results from most outcomes that are described in the methods section of the study are actually reported. Only results on walking distance are not reported, and this is an outcome measure that is rarely reported in comparable studies. However, in their final publication (Klein 2006), the study authors report on the proportion of patients that are symptom‐free as defined by the Fontaine classification, which is an outcome measure that is not mentioned in any of their previous publications or in the methods section, and which is the one outcome in this publication that the authors report to be statistically significant.
Other bias	Low risk	The original trial was supported by a PIONIER award from the Netherlands Organization for Scientific Research and a grant from the Commission of Investigative Medicine of the Dutch National Health Insurance Council. One article on long‐term results was funded by Cordis, the company that manufactures Palmaz stents. However, it is stated that the investigators were in full control of the data.

STAG trial.

Study characteristics
Methods	RCT comparing PS and primary PTA with selective stenting. Secondary stenting was performed in cases in which there was no flow whatsoever in the treated segment, or if complications warranted stent placement. In 16% of lesions, stenting was required.
Participants	This study was performed in 6 major hospitals in the UK. Inclusion criterion was iliac occlusion. There was no age limit. Exclusion criteria: occlusions < 8 cm were excluded It is unclear how many potentially eligible patients were identified. 118 patients were randomised and 112 analysed (6 excluded due to major protocol violations) (number of lesions not reported); 57 in PS, 55 in PTA Sex: PS 72% male (41/57), PTA 64% male (35/55) Age: PS 60.2 (8.9), PTA 60.6 (10.5) Disease severity: Rutherford classification: PS I: 6% (3), II: 46% (24), III: 44% (23), IV: 2% (1), V: 2% (1) PTA I: 18% (9), II: 31% (16), III: 49% (25), IV: 2% (1), V: 0% (0) Co‐morbidities/risk factors ‐ Tobacco use: PS 44% (24/55), PTA 38% (21/55) ‐ Diabetes: PS 16% (9/57), PTA 5% (3/55) ‐ Hypertension: PS 23% (13/57), PTA 20% (11/55) ‐ Cerebrovascular history: not reported ‐ Dyslipidaemia: PS 53% (28/53), PTA 47% (23/50) Location: not reported
Interventions	PS: no details are given on the technique used for PS PTA: no details are given on the technique used for primary PTA. Secondary stenting was performed in case of no forward flow, or complications that could be resolved by the use of a stent. If any flow, regardless of residual stenosis or pressure gradient, no stent was placed. In 38% of lesions, stenting was required. Before intervention aspirin was started, or dipyridamole if patients were aspirin‐intolerant. The trial was conducted before the introduction of statins and thienopyridines. After arterial access had been achieved, 5000 units of UFH were given.
Outcomes	Primary outcome: ‐ Technical success ‐ presence of antegrade flow through the treated segment (patients in the PTA group who required a stent were categorised as having a technical failure) ‐ Major complications ‐ resulting in death, permanent disability, unplanned amputation due to the intervention, an unexpected or unplanned secondary procedure (excluding secondary stent placement), delayed hospital discharge or blood transfusion Secondary outcomes: ‐ Patency ‐ as assessed by angiography at 1 and 2 years
Funding	NHS R&D Regional Programme Register ‐ Department of Health (UK)
Declarations of interest	No conflicts
Notes	This trial was stopped prematurely due to a significantly higher rate of distal embolisation in the PTA group.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were assigned using randomly allocated, independently constructed envelopes
Allocation concealment (selection bias)	Low risk	Patients were assigned using randomly allocated, independently constructed envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	"It was not possible to blind the operator from the assigned treatment group." It is unclear whether patients were blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	This is not reported
Incomplete outcome data (attrition bias) All outcomes	High risk	Only 83 patients underwent a 1‐year angiography, and only 47 patients underwent a 2‐year angiography. It is unclear why these patients were lost to follow‐up (i.e. death, migration, withdrawal)
Selective reporting (reporting bias)	Unclear risk	Outcome measures were used according to the most recent internationally recognised reporting standards at the time of the study
Other bias	Low risk	This study was funded by Trent Regional Health Authority. The study authors declare no conflict of interest

ABI: ankle brachial index
CIA: common iliac artery
EIA: external iliac artery
IC: intermittent claudication
PS: primary stenting
PTA: percutaneous transluminal angioplasty
RCT: randomised controlled trial
UFH: unfractionated heparin

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Bekken 2012	This is a study protocol, no data have been published yet. This study will not compare PTA with PS but instead compare PS with two types of stents (bare metal versus covered).
Bolt 2019	This study does not compare PTA with PS but instead compares duplex‐guided with angiographic endovascular treatment of the iliac arteries.
Choi 2016	This is a study protocol, no data have been published yet. This study will not compare PTA with PS but instead compare primary stenting with two types of stents (balloon‐expandable versus self‐expanding).
Dake 2007	This study does not evaluate iliac arteries but instead looks at superficial femoral and popliteal arteries.
Deloose 2017	This is not a RCT but instead a prospective series of patients treated with primary stenting.
Hunt 2017	This is a study protocol, no data have been published yet. This study does not evaluate iliac arteries but instead looks at superficial femoral and popliteal arteries.
Katzen 2006	This study does not evaluate iliac arteries but instead looks at superficial femoral and popliteal arteries.
Kauffmann 1991a	This is a quasi‐randomised controlled trial. No peer‐reviewed publication was published on the final study data. We contacted study authors for further information but received no reply.
Krankenberg 2017	This study does not compare PTA with PS but instead compares PS with two types of stents (balloon‐expandable versus self‐expanding).
Mwipatayi 2011	This study does not compare PTA with PS but instead compares PS with 2 type of stents (bare metal versus covered).
NCT02209350	This is a study protocol, no data have been published yet. This study will not compare PTA with PS but instead compare PS of the iliac artery with aorta‐femoral bypass.
NCT03315884	This is a study protocol, no data have been published yet. This study will not compare PTA with PS but instead compare PS and common femoral artery stenting with PS and common femoral artery patch plasty.
NCT03414515	This is a study protocol, no data have been published yet. This study is not a RCT but instead a non‐randomised observational series of patients treated with PTA or PS.
NCT04023370	This is a study protocol, no data have been published yet. This study will not compare PTA with PS but instead compare PS with two types of stents (bare metal versus covered).

PS: primary stenting
PTA: percutaneous transluminal angioplasty

Differences between protocol and review

2020 version

In keeping with current Cochane recommendations, we have added a 'Summary of findings' table to present the main findings of this review and assessed the certainty of the evidence using GRADE criteria. We reassessed and reordered primary and secondary outcome measures to reflect current clinical relevance.

2015 version

The Jadad scoring system (Jadad 1996) has been superseded by the 'Risk of bias' tool (Higgins 2011).
We have added the secondary outcome 'reinterventions of the treated lesion' because we believe that this is a highly clinically relevant outcome.
We have updated the secondary outcome 'revision of amputation level' to 'major amputation‐free survival', defined as survival without above‐ankle amputation. We believe this is a more clinically relevant outcome, and is more widely used in trials concerning critical limb ischaemia.
We have rephrased the 'Types of participants' and 'Types of interventions' to reflect current terminology.

Contributions of authors

HJ: article selection, data extraction, writing of the review
JB: article selection, data extraction, writing of the review
NA: proofreading of the review
CJH: proofreading of the review
VvW: proofreading of the review
BF: resolved disagreements concerning article selection and data extraction, proofreading of the review

Sources of support

Internal sources

• No sources of support supplied

External sources

• Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK

  The Cochrane Vascular editorial base is supported by the Chief Scientist Office.

Declarations of interest

HJ: none known
JB: currently involved in an ongoing RCT comparing covered versus bare‐metal balloon‐expandable stents for advanced peripheral arterial occlusive disease (PAOD) in the common iliac artery (Bekken 2012). This study does employ primary stenting (Getinge AB, Gothenburg, Sweden). No payments to our institutions have occurred in the last 36 months.
NA: none known
CJH: none known
VvW: none known
BF: currently involved in an ongoing RCT comparing covered versus bare‐metal balloon‐expandable stents for advanced PAOD in the common iliac artery (Bekken 2012). This study does employ primary stenting (Getinge AB, Gothenburg, Sweden). No payments to our institutions have occurred in the last 36 months.

New search for studies and content updated (no change to conclusions)