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Endoluminal stents for iliac and infrainguinal arterial disease

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Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

The primary objective is to assess the effects of different types of endoluminal stents (for example, bare metal, covered, drug‐eluting) against each other for restoration of patency in iliac, SFA, popliteal and infrapopliteal artery occlusions or stenoses.

The secondary objectives are to assess the effectiveness of different types of stents in a) different participants (that is participants with claudication compared with participants with critical limb ischaemia) and b) different types of lesions based on the Trans‐Atlantic Inter‐Society Consensus II for each anatomical region (iliac, SFA, popliteal and infrapopliteal) (Dormandy 2000; Jaff 2015). In the absence of TASC II classifications, we will perform subgroup analyses with the lesions stratified into short (≤ 10 cm) or long (> 10 cm) stenosis or occlusion.

Background

Description of the condition

Peripheral arterial disease (PAD) of the lower limb is a common, important manifestation of systemic atherosclerosis and it can occur in up to 3% to 10% of the general population. This increases to 15% to 20% in people over 70 years of age (Criqui 2015; ESO 2011; Fowkes 2013; Selvin 2004). Based on epidemiological data, 202 million people globally were living with PAD in 2010, the majority in lower‐income countries (Fowkes 2013).

The most common site of PAD is the superficial femoral artery (SFA) (Fowkes 1991), but it is also found in the iliac, popliteal and infrapopliteal arteries. While most patients with PAD are asymptomatic, many have intermittent claudication, or acute or chronic critical limb ischaemia (CLI) (ischaemic rest pain, ulceration, gangrene and tissue loss) (Rutherford 1997). Optimal and cost‐effective treatment is important because peripheral arterial disease significantly impairs quality of life and can result in amputation of the limb (Dormandy 1994).

Various therapeutic modalities have been used in the management of iliac, SFA and popliteal artery occlusions or stenoses. These range from non‐invasive exercise therapy to angioplasty (Fowkes 2008; Lane 2014). Percutaneous angioplasty (PTA) with endoluminal prosthetic stent insertion is becoming increasingly commonplace in the management of iliac, SFA, popliteal and infrapopliteal artery occlusive disease of the lower limbs (Bekken 2015; Bosiers 2012; Chowdhury 2014; Hsu 2011; Rastan 2012). In the management of ischaemic femoro‐popliteal atherosclerotic disease, it has been shown that primary stenting does not appear to confer any advantage in maintaining vessel patency post‐PTA (Chowdhury 2014). The exception to this is for disease with lesions of more than 10 cm in length. For lesions of more than 10 cm, primary stenting has been reported to confer an advantage at both six months and one year (Schillinger 2006). Primary stenting has been shown to have an advantage over angioplasty alone in preventing immediate technical failure. To date, there have been several non‐randomised studies and a few randomised studies examining primary stent usage (Cejna 2001; Duda 2005; Grimm 2001; Schillinger 2006; Vroegindeweij 1997).

Description of the intervention

In the treatment of iliac, SFA, popliteal and infrapopliteal artery occlusive disease, where it is appropriate the use of different types of stent is becoming more commonplace. Examples of the types of stent used are bare metal, stainless steel, nitinol, covered (PTFE), drug‐eluting, heparin‐bonded and, more recently, biodegradable stents.

How the intervention might work

Traditionally accepted indications for stenting have been as optional salvage (secondary) procedures for lesions that have had angioplasty performed but still remain significantly stenosed (immediate technical failure), for recurrent stenoses or occlusions (primary patency failure) and for complications of angioplasty such as intimal dissection or perforation.

Why it is important to do this review

We believe that an evidence‐based evaluation and review of the different types of stent used following angioplasty in iliac, lower limb SFA, popliteal and infrapopliteal artery occlusive disease is timely as it will address the efficacy and safety issues and help to guide clinical practice.

Objectives

The primary objective is to assess the effects of different types of endoluminal stents (for example, bare metal, covered, drug‐eluting) against each other for restoration of patency in iliac, SFA, popliteal and infrapopliteal artery occlusions or stenoses.

The secondary objectives are to assess the effectiveness of different types of stents in a) different participants (that is participants with claudication compared with participants with critical limb ischaemia) and b) different types of lesions based on the Trans‐Atlantic Inter‐Society Consensus II for each anatomical region (iliac, SFA, popliteal and infrapopliteal) (Dormandy 2000; Jaff 2015). In the absence of TASC II classifications, we will perform subgroup analyses with the lesions stratified into short (≤ 10 cm) or long (> 10 cm) stenosis or occlusion.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (single or multicentre) that compare different stent types for occlusions or stenoses of the iliac, SFA, popliteal or infrapopliteal arteries. We will exclude studies that assess stent usage in aneurysms or aneurysmal lesions as these are examined in other reviews (Duffy 2015; Rolph 2015). We will exclude studies that compare stenting against angioplasty as these are also examined in other reviews (Bekken 2015; Chowdhury 2014; Hsu 2011).

We will consider trials that have been published in full or have results presented in abstract form. We will include abstracts only if there are sufficient data for analysis, full publication is planned or unpublished data are available on file for review and analysis.

In addition, we will consider randomised controlled trials conducted by stent device manufacturers where data are on file but not published.

Types of participants

We will include adult patients (> 18 years of age) with symptomatic PAD affecting the iliac, SFA, popliteal and infrapopliteal arteries who undergo endoluminal stenting. This will include people with claudication and critical ischaemia. This will be defined as Fontaine stages IIa through to IV or Rutherford classification 1‐6 (Fontaine 1954; Rutherford 1997). Where possible, the results will be stratified according to either claudication or critical limb ischaemia.

Types of interventions

We plan to assess the effects of primary stenting of each anatomical region (i.e. iliac, SFA, popliteal and infrapopliteal artery). We will present the effects by each anatomical region separately. We will compare the efficacy of one type of stent against another, for example bare metal stent versus covered stent.

Types of outcome measures

Primary outcomes

The primary outcomes are the following.

  • Primary unassisted vessel patency failure over a follow‐up period of one and two years. This is defined as the first restenosis (≥ 50%) following the initial intervention, as measured using duplex ultrasonography, angiography, computed tomography angiogram (CTA) or magnetic resonance angiogram (MRA).

  • Primary assisted patency defined as patency after re‐intervention of a stent stenosis.

  • Secondary patency defined as patency after re‐intervention of a stent occlusion.

  • Quality of life (as assessed by the individual studies) at 30 days, one year and two years.

Secondary outcomes

The secondary outcomes are the following.

  • Limb salvage rates/amputation at 30 days, one year and two years where possible.

  • Change in functional status, for example claudication distance (pain‐free walking distance) and treadmill exercise performance (maximum walking distance).

  • Change in ankle‐brachial index (ABI) values post‐stent placement.

  • Morbidity rates.

    • Stent‐related: stent failure/fracture, stent migration, stent infection, stent occlusion.

    • Procedural‐related: groin haematoma, wound infection, wound bleeding, vessel rupture/perforation, vessel wall dissection, distal emboli.

    • General morbidity: development of acute myocardial infarct, acute renal failure, chronic renal failure, cerebrovascular event.

  • Mortality at 30 days, one year and two years.

  • Change in translesional endoluminal pressure (translesional pressure gradient) post‐stent placement.

Search methods for identification of studies

We will only include studies in the review that have been conducted since 1 January 1986. The rationale for this is the fact that angioplasty and concomitant prosthetic stents have only been widely used in lower limb peripheral vascular disease since the mid 1980s. There will be no restriction on language. We will make attempts to translate non‐English language studies for inclusion in the analyses.

Electronic searches

The Cochrane Vascular Information Specialist (CIS) will search the following databases for relevant trials:

  • the Cochrane Vascular Specialised Register;

  • the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online.

See Appendix 1 for details of the search strategy that will be used to search CENTRAL.

The Cochrane Vascular Specialised Register is maintained by the CIS and is constructed from weekly electronic searches of MEDLINE Ovid, Embase Ovid, CINAHL and AMED, and through handsearching of relevant journals. The full list of the databases, journals and conference proceedings that have been searched, as well as the search strategies used, are described in the Specialised Register section of the Cochrane Vascular module in the Cochrane Library (www.cochranelibrary.com).

The CIS will search the following trial registries for details of ongoing and unpublished studies:

Searching other resources

In addition, the review authors will search conference proceedings and abstracts presented at key vascular surgery/medicine meetings to identify relevant studies. These meetings will include:

  • the Society of Vascular Surgeons (SVS) American meeting;

  • the Society of Vascular Surgeons of Great Britain and Ireland (UK) meeting;

  • the International Congress of the Asian Society of Vascular Surgeons (Asia‐Pacific);

  • the International Union of Angiology meeting (Europe);

  • other Interventional Cardiology and Interventional Radiology meetings.

We will also contact the major stent device manufacturers to obtain information on unpublished data and any ongoing trials.

The companies that we will contact include:

  • Abbott Vascular;

  • Boston Scientific;

  • Cook Incorporated;

  • Cordis;

  • Edwards Life Sciences;

  • Johnson & Johnson;

  • Medtronic;

  • WL Gore & Associate.

Data collection and analysis

Selection of studies

Two review authors (AW, KP) will independently select trials for inclusion. We will resolve any differences in consultation with a third author (GS or PW).

Data extraction and management

Two review authors (AW, KP) will independently extract data according to a fixed protocol as per the extraction forms provided by Cochrane Vascular. Both review authors will crosscheck each other's data abstractions with regular quality audits. Any differences will also be resolved in consultation with GS and PW, and after group consensus. If necessary, we will contact the authors of studies to resolve disputes. We will also contact the authors of published or unpublished trials, abstracts, presentations and field data should additional information be required.

Assessment of risk of bias in included studies

Two review authors (AW, KP) will independently assess the included studies using the Cochrane tool for assessing risk of bias (Higgins 2011). This tool covers: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting and other sources of bias. We will assess each of these domains as either 'high', 'low' or 'unclear' risk of bias according to Higgins 2011 and provide support for each judgement. We will present the judgements in a 'Risk of bias' table.

Measures of treatment effect

Dichotomous data

For homogenous binary outcomes, we will calculate the risk ratio (RR) with a 95% confidence interval (CI) using the fixed‐effect model. Where possible, we will calculate the number needed to treat to benefit (NNTB). For heterogeneous data the RR is calculated using the DerSimonian‐Laird random‐effects model (DerSimonian 1986).

Continuous data

We will use parametric tests to analyse continuous data. However, we will apply the following criteria:

  • means and standard deviations/errors have to be obtainable;

  • when a scale starts from a finite number (such as zero), the data must be within a normal distribution (i.e. the mean must be within two standard deviations).

We will report data not meeting these standards under 'Other data types' in the 'Effects of interventions' section, where we will analyse the data using appropriate non‐parametric tests.

Unit of analysis issues

The individual participant will be the unit of analysis.

Dealing with missing data

We will contact study authors for any missing or unclear data.

We will exclude data with more than 10% incomplete or missing entries for each outcome from the analyses. This is to reduce bias due to issues such as poor follow‐up or inaccurate data collection.

Where possible, we will analyse data on an intention‐to‐treat (ITT) basis. We will use the negative assumption for those lost to follow‐up. For example, in determining restenosis rates, we will consider those lost to follow‐up as re‐stenosed. This assumption may vary depending on the outcome but we will pre‐state all assumptions and test them in a sensitivity analysis. The exception to this assumption are deaths, which we will not count as losses of contact and, conversely, we will not count losses to follow‐up as deaths.

Assessment of heterogeneity

We will use the Chi² of heterogeneity to determine whether outcomes are heterogenous. For this test, we will determine statistical significance at a level of P = 0.1. If significance is determined, we will carry out a sensitivity analysis to assess the effect of particular studies on the effect estimate.

Assessment of reporting biases

If sufficient studies (> 10) are available we will create a funnel plot (trial effect against trial size) to investigate the likelihood of overt publication bias or other variables associated with skewed funnel plots (Higgins 2011).

Data synthesis

One review author will enter the abstracted data into RevMan 5 (RevMan 2014). A second review author will check the data.

We will use the fixed‐effect model for meta‐analysis when there is no heterogeneity and the random‐effects model when heterogeneity exists (Chi² P < 0.10). We will present the results in forest plots.

Subgroup analysis and investigation of heterogeneity

We will assess the effectiveness of each stent type against other stents according to anatomical regions (iliac, SFA, popliteal and infrapopliteal). We will undertake subgroup analyses for patients stratified by the following factors where possible:

  • Disease severity: claudication versus critical ischaemia.

  • Types of lesion by TASC II (Dormandy 2000; Jaff 2015).

  • Types of lesion by lesion length: long segment (> 10 cm) versus short segment (≤ 10 cm).

  • Stenosis versus occlusion.

  • Single‐segment stenting versus multi‐segment stenting.

  • Primary lesion versus recurrent disease.

  • Diabetics versus non‐diabetics.

Sensitivity analysis

We will perform sensitivity analyses by excluding those studies that we deem to be at high risk of bias for sequence generation and allocation concealment. We will carry out further sensitivity analysis to assess the effect of particular studies on the effect estimate if heterogeneity is identified as significant (Chi² P < 0.10). We will also carry out and test per‐protocol analyses in the form of a sensitivity analysis and compare the results with the results obtained from the ITT analyses.

Summary of findings

We will present the main findings of the review concerning the quality of evidence, the magnitude of effect of the interventions examined and the sum of available data for the different comparisons and primary outcomes of this review in a 'Summary of findings' table, according to the GRADE principles as described by Higgins 2011 and Atkins 2004. We will use the GRADEprofiler (GRADEpro) software to assist in the preparation of the 'Summary of findings' table (www.guidelinedevelopment.org). An example 'Summary of findings' table is presented in Table 1. Using the GRADE approach, we will assess the quality of the body of evidence for each outcome as high, moderate, low or very low based on the following criteria: risk of bias, inconsistency, indirectness, imprecision and publication bias.

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Table 1. Example 'Summary of findings' table

Bare metal stent compared with covered stent for restoration of patency in iliac artery occlusion or stenosis

Patient or population: people with iliac artery occlusion or stenosis

Settings: hospital

Intervention: bare metal stent

Comparison: covered stent

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Covered stent

Bare metal stent

Primary unassisted vessel patency failure

[follow‐up]

Study population

RR

⊕⊝⊝⊝
very low

⊕⊕⊝⊝
low

⊕⊕⊕⊝
moderate

⊕⊕⊕⊕
high

[value] per 1000

[value] per 1000
([value] to [value])

Primary assisted patency

[follow‐up]

Study population

RR

⊕⊝⊝⊝
very low

⊕⊕⊝⊝
low

⊕⊕⊕⊝
moderate

⊕⊕⊕⊕
high

[value] per 1000

[value] per 1000
([value] to [value])

Secondary patency

[follow‐up]

Study population

RR

⊕⊝⊝⊝
very low

⊕⊕⊝⊝
low

⊕⊕⊕⊝
moderate

⊕⊕⊕⊕
high

[value] per 1000

[value] per 1000
([value] to [value])

Quality of life parameter

[range of scale or scale description]

[follow‐up]

The mean quality of life parameter ranged across control groups from
[value][measure]

The mean quality of life parameter in the intervention groups was
[value] [lower/higher]
[(value to value lower/higher)]

⊕⊝⊝⊝
very low

⊕⊕⊝⊝
low

⊕⊕⊕⊝
moderate

⊕⊕⊕⊕
high

*The basis for the assumed risk is the average risk in the covered stent group (i.e. the number of participants with events divided by total number of participants of the covered stent group included in the meta‐analysis). The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

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

Table 1. Example 'Summary of findings' table

Bare metal stent compared with covered stent for restoration of patency in iliac artery occlusion or stenosis

Patient or population: people with iliac artery occlusion or stenosis

Settings: hospital

Intervention: bare metal stent

Comparison: covered stent

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Covered stent

Bare metal stent

Primary unassisted vessel patency failure

[follow‐up]

Study population

RR

⊕⊝⊝⊝
very low

⊕⊕⊝⊝
low

⊕⊕⊕⊝
moderate

⊕⊕⊕⊕
high

[value] per 1000

[value] per 1000
([value] to [value])

Primary assisted patency

[follow‐up]

Study population

RR

⊕⊝⊝⊝
very low

⊕⊕⊝⊝
low

⊕⊕⊕⊝
moderate

⊕⊕⊕⊕
high

[value] per 1000

[value] per 1000
([value] to [value])

Secondary patency

[follow‐up]

Study population

RR

⊕⊝⊝⊝
very low

⊕⊕⊝⊝
low

⊕⊕⊕⊝
moderate

⊕⊕⊕⊕
high

[value] per 1000

[value] per 1000
([value] to [value])

Quality of life parameter

[range of scale or scale description]

[follow‐up]

The mean quality of life parameter ranged across control groups from
[value][measure]

The mean quality of life parameter in the intervention groups was
[value] [lower/higher]
[(value to value lower/higher)]

⊕⊝⊝⊝
very low

⊕⊕⊝⊝
low

⊕⊕⊕⊝
moderate

⊕⊕⊕⊕
high

*The basis for the assumed risk is the average risk in the covered stent group (i.e. the number of participants with events divided by total number of participants of the covered stent group included in the meta‐analysis). The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

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

Figuras y tablas -
Table 1. Example 'Summary of findings' table