Angioplasty versus bare metal stenting for superficial femoral artery lesions

  • Review
  • Intervention

Authors


Abstract

Background

Lower limb peripheral arterial disease (PAD) is a common, important manifestation of systemic atherosclerosis. Stenoses or occlusions in the superficial femoral artery may result in intermittent claudication or even critical ischaemia, which may be treated by balloon angioplasty with or without stenting. This is the first update of a review published in 2009.

Objectives

The primary aim was to determine the effect of percutaneous transluminal angioplasty (PTA) compared with PTA with bare metal stenting for superficial femoral artery (SFA) stenoses on vessel patency in people with symptomatic (Rutherford categories1 to 6; Fontaine stages II to IV) lower limb peripheral vascular disease.

In addition, we assessed the efficacy of PTA and stenting in improving quality of life, ankle brachial index and treadmill walking distance.

Search methods

For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched August 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 6).

Selection criteria

Randomised trials of angioplasty alone versus angioplasty with bare metal stenting for the treatment of superficial femoral artery stenoses.

Data collection and analysis

Two review authors (MC, CT) independently selected suitable trials, assessed trial quality and extracted data. Furthermore, these two review authors performed assessments of methodological quality and wrote the final manuscript. The third review author (ADM) cross-checked all stages of the review process.

Main results

We include three new studies in this update, making a total of 11 included trials with 1387 participants. The average age was 69 years and all trials included men and women. Participants were followed for up to two years. There was an improvement in primary duplex patency at six and 12 months in participants treated with PTA plus stent over lesions treated with PTA alone (six months: odds ratio (OR) 2.90, 95% confidence interval (CI) 1.17 to 7.18, P = 0.02, six studies, 578 participants; 12 months: OR 1.78, 95% CI 1.02 to 3.10, P = 0.04, nine studies, 858 participants). This was lost by 24 months (P = 0.06). There was a significant angiographic patency benefit at six months (OR 2.49, 95% CI 1.49 to 4.17, P = 0.0005, four studies, 329 participants) which was lost by 12 months (OR 1.30, 95% CI 0.84 to 2.00, P = 0.24, five studies, 384 participants). Ankle brachial index (ABI) and treadmill walking distance showed no improvement at 12 months (P = 0.49 and P = 0.57 respectively) between participants treated with PTA alone or PTA with stent insertion. Three trials (660 participants) reported quality of life, which showed no significant difference between participants treated with PTA alone or PTA with stent insertion at any time interval. Antiplatelet therapy protocols and inclusion criteria regarding affected arteries between trials showed marked heterogeneity.

Authors' conclusions

Although there was a short-term gain in primary patency there was no sustained benefit from primary stenting of lesions of the superficial femoral artery in addition to angioplasty. Future trials should focus on quality of life for claudication and limb salvage for critical ischaemia.

Résumé scientifique

Angioplastie versus pose de stent métallique nu dans le traitement des lésions de l'artère fémorale superficielle

Contexte

La maladie artérielle périphérique (MAP) des membres inférieurs est une manifestation importante et courante de l'athérosclérose systémique. Les sténoses ou occlusions de l'artère fémorale superficielle peuvent entraîner une claudication intermittente ou même une ischémie aiguë, qui peuvent être traitées par une angioplastie par ballonnet avec ou sans pose de stent. Ceci est la première mise à jour d'une revue publiée en 2009.

Objectifs

L'objectif principal était de déterminer l'effet de l'angioplastie transluminale percutanée (ATP) par rapport à l'ATP avec pose de stent métallique nu pour le traitement des sténoses de l'artère fémorale superficielle (AFS) sur la perméabilité des vaisseaux chez les personnes atteintes de maladie vasculaire périphérique des membres inférieurs symptomatique (Rutherford catégories 1 à 6 ; Fontaine stades II à IV).

En outre, nous avons évalué l'efficacité de l'ATP avec pose de stent dans l'amélioration de la qualité de vie, de l'indice tibio-brachial et de la distance de marche sur tapis roulant.

Stratégie de recherche documentaire

Pour cette mise à jour, le coordinateur de recherche d'études du groupe Cochrane sur les maladies vasculaires périphériques a effectué des recherches dans le registre spécialisé (dernière recherche en août 2013) et le registre Cochrane des essais contrôlés (CENTRAL) (2013, numéro 6).

Critères de sélection

Essais randomisés portant sur l'angioplastie seule versus angioplastie avec pose de stent métallique nu pour le traitement des sténoses de l'artère fémorale superficielle.

Recueil et analyse des données

Deux auteurs de la revue (MC, CT) ont indépendamment sélectionné les essais adéquats, évalué leur qualité et extrait des données. En outre, ces deux auteurs de la revue ont évalué la qualité méthodologique et écrit le manuscrit final. Le troisième auteur de la revue (ADM) a recoupé tous les stades du processus de revue.

Résultats principaux

Nous avons inclus trois nouvelles études dans cette mise à jour, donnant un total de 11 essais inclus, avec 1 387 participants. L'âge moyen était de 69 de ans et tous les essais incluaient des hommes et des femmes. Les participants ont été suivis pendant une période maximale de deux ans. Il y avait une amélioration dans la perméabilité primaire évaluée par échographie duplex à six et à 12 mois chez les participants traités par ATP plus stent par rapport aux lésions traitées avec l'ATP seule (six mois : rapport des cotes (RC) 2,90, intervalle de confiance (IC) à 95 % 1,17 à 7,18, P = 0,02, six études, 578 participants ; 12 mois : RC 1,78, IC à 95 % 1,02 à 3,10, P = 0,04, neuf études, 858 participants). Cet avantage avait disparu à 24 mois (P = 0,06). Il y avait un bénéfice significatif dans la perméabilité évaluée par angiographie à six mois (RC 2,49, IC à 95 % 1,49 à 4,17, P = 0,0005, quatre études, 329 participants) qui avait disparu à 12 mois (RC 1,30, IC à 95 % 0,84 à 2,00, P = 0,24, cinq études, 384 participants). L'indice tibio-brachial (ITB) et la distance de marche sur tapis roulant ne montraient aucune amélioration à 12 mois (P = 0,49 et P = 0,57 respectivement) entre les participants traités par l'ATP seule ou par l'ATP avec pose de stent. Trois essais (660 participants) avaient rapporté la qualité de vie ; celle-ci n'a montré aucune différence significative entre les participants traités par l'ATP seule ou par l'ATP avec pose de stent, quel que soit l'intervalle de temps. Les protocoles de traitement antiplaquettaire et les critères d'inclusion concernant les artères affectées ont montré une hétérogénéité marquée entre les essais.

Conclusions des auteurs

Bien qu'il y ait eu à court terme un gain de la perméabilité primaire, aucun bénéfice soutenu n'a été observé suite à la pose de stent primaire sur des lésions de l'artère fémorale superficielle en plus de l'angioplastie. Les essais futurs devraient se concentrer sur la qualité de vie pour la claudication et le sauvetage du membre pour l'ischémie aiguë.

Plain language summary

Angioplasty versus angioplasty plus stenting for lesions of the superficial femoral artery

Intermittent claudication is pain in the leg that is brought on by walking and which is relieved by rest. The pain is a result of insufficient blood flow to the muscles of the leg due to narrowing of the arteries by atherosclerosis. People who have narrowing of the main artery in the thigh, the superficial femoral artery, and intermittent claudication which severely restricts their quality of life or causes dangerous tissue changes in the leg may undergo a procedure known as angioplasty to widen this narrowing. This procedure involves passing a balloon into the narrowed segment and inflating the balloon to push the artery open. In addition to this, a cylindrical piece of metal mesh called a stent may be inserted at the site where the artery has been pushed open with the aim of holding the narrowing open in the future. While stents work well in the arteries of the heart and in other arteries, it is not clear whether adding stents following angioplasty to narrowings of the superficial femoral artery gives any benefit to the patient.

We identified 11 randomised controlled trials with a total of 1387 participants. Their average age was 69 years and all trials included men and women. The participants were randomised to have either balloon angioplasty alone or balloon angioplasty with stent placement. At two years, blood flowing through the narrowing in the arteries was no greater in participants with a stent inserted than in those without. There was a small improvement in the distance that the participants with a stent could walk up to one year later. However, when asked about their quality of life there was no improvement, whether a stent was placed or not, up to one year later. There were differences in the included trials; in some trials people with narrowings in other leg arteries were included. There were also differences between trials in the blood thinning drugs given after stent placement, which may change results, as these agents are important in keeping stents working in other parts of the body. These factors led us to the conclusion that there is a small benefit to adding a stent when performing balloon angioplasty for people in whom balloon angioplasty fails. However, there is insufficient evidence to support this approach as routine practice for everyone and future trials should examine whether subgroups of patients may benefit from stenting.

Résumé simplifié

L'angioplastie par rapport à l'angioplastie plus pose d'un stent pour le traitement des lésions de l'artère fémorale superficielle

La claudication intermittente est une douleur dans la jambe qui est provoquée par la marche et est soulagée par le repos. La douleur est le résultat d'un apport sanguin insuffisant dans les muscles de la jambe dû à un rétrécissement des artères en raison d'une athérosclérose. Les personnes qui présentent un rétrécissement de l'artère principale de la cuisse, l'artère fémorale superficielle, et une claudication intermittente qui réduit gravement leur qualité de vie ou provoque de dangereux changements tissulaires dans la jambe peuvent subir une procédure appelée angioplastie pour élargir ce rétrécissement. Cette procédure consiste à faire passer un ballonnet dans le segment rétréci et à gonfler ce ballonnet pour écarter et dégager l'artère. De plus, une pièce cylindrique en treillis métallique appelée endoprothèse vasculaire ou stent peut être insérée au point où l'artère a été écartée afin de maintenir le rétrécissement ouvert par la suite. Si les stents fonctionnent bien dans les artères du cœur et les autres artères, on ignore si l'ajout de stents après une angioplastie de rétrécissements de l'artère fémorale superficielle apporte des bénéfices pour le patient.

Nous avons identifié 11 essais contrôlés randomisés avec un total de 1 387 participants. Leur âge moyen était de 69 ans et tous les essais incluaient des hommes et des femmes. Les participants ont été aléatoirement repartis pour subir soit une angioplastie par ballonnet seule, soit une angioplastie par ballonnet avec pose d'un stent. A deux ans, la circulation du sang par le rétrécissement des artères n'a pas été supérieure chez les participants avec un stent que chez ceux n'en ayant pas reçu. On a observé une légère amélioration de la distance que les participants avec un stent pouvaient parcourir à pied jusqu'à un an après l'intervention. Cependant, lorsqu'ils ont été interrogés sur leur qualité de vie, ils ont indiqué une absence d'amélioration, avec ou sans la pose d'un stent, jusqu'à un an après l'intervention. Il y a eu des différences entre les essais inclus ; dans certains essais, les personnes présentant des rétrécissements dans d'autres artères des jambes ont été incluses. Il y a également eu des différences entre les essais au niveau des médicaments anticoagulants administrés après la pose du stent, ce qui pourrait changer les résultats, car ces agents sont importants pour maintenir le fonctionnement des stents dans d'autres parties du corps. Ces facteurs nous ont conduit à la conclusion qu'il existait un léger bénéfice à l'ajout d'un stent lors de la réalisation d'une angioplastie par ballonnet pour les personnes chez qui l'angioplastie par ballonnet échoue. Cependant, il n'existe pas suffisamment de preuves pour soutenir cette approche en pratique de routine pour tous les patients et les futurs essais devront examiner si des sous-groupes de patients pourraient bénéficier de la pose d'un stent.

Notes de traduction

Traduit par: French Cochrane Centre 31st August, 2014
Traduction financée par: Financeurs pour le Canada : Instituts de Recherche en Santé du Canada, Ministère de la Santé et des Services Sociaux du Québec, Fonds de recherche du Québec-Santé et Institut National d'Excellence en Santé et en Services Sociaux; pour la France : Ministère en charge de la Santé

Background

Description of the condition

Lower limb peripheral arterial disease (PAD) is a common, important manifestation of systemic atherosclerosis. It occurs in 3% to 10% of the population, increasing to 15% to 20% in people over 70 years of age (Selvin 2004). The most common site of PAD is the superficial femoral artery (SFA) (Fowkes 1991). While most people with PAD are asymptomatic, many have intermittent claudication, chronic critical limb ischaemia or acute critical limb ischaemia. As a result, PAD significantly impairs quality of life and is the most common cause of lower limb amputation in the western world. Successful treatment of PAD is therefore of the utmost importance.

Description of the intervention

Superficial femoral artery disease may be treated by a number of modalities depending on the length of lesion. Exercise therapy and best medical therapy are the best suggested methods of initial therapy for people with claudication (NICE 2012), while rest pain and tissue loss is treated more aggressively with early intervention. For lesions less than 10 cm long in symptomatic patients, the most common treatment is currently percutaneous transluminal angioplasty (PTA) with or without the use of stents. While PTA can result in initial technical success rates of more than 95%, late clinical failure remains an important concern.

Why it is important to do this review

The recognition that treatment for PAD varies by centre has led to the creation of continually updated international guidelines (NICE 2012; Norgren 2007). These guidelines currently recommend the use of PTA as a primary treatment in SFA lesions less than 10 cm long with stenting for acute primary failure. However, recent randomised control trials have results conflicting with these recommendations and, in some cases, with one another (Vienna Absolute Trial; Zdanowski 1999).

Objectives

The primary aim was to determine the effect of percutaneous transluminal angioplasty (PTA) compared with PTA with stenting for superficial femoral artery (SFA) stenoses on vessel patency in people with symptomatic (Rutherford categories 1 to 6; Fontaine stages II to IV) lower limb peripheral vascular disease.

In addition, we assessed the efficacy of PTA and stenting in improving quality of life as assessed by the trialists, ankle brachial index (ABI) and treadmill walking distance.

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCTs) that compared percutaneous angioplasty alone with percutaneous angioplasty plus stenting.

Types of participants

People with intermittent claudication or critical limb ischaemia (Rutherford categories 1 to 6; Fontaine stages II to IV) (Fontaine 1954; Rutherford 1997). We considered people with TASC (Norgren 2007) A and B superficial femoral artery (SFA) lesions. TASC A lesions are single stenoses ≤ 10 cm in length or single occlusions ≤ 5 cm in length, while TASC B lesions are multiple stenoses or occlusions each ≤ 5 cm, a single stenosis or occlusion ≤ 15 cm not involving the infrageniculate popliteal artery, and heavily calcified occlusions ≤ 5 cm in length. The definition of TASC B lesions also includes single or multiple lesions in the absence of continuous tibial vessels and single popliteal stenoses, which are not considered by interventions included in this review.

Types of interventions

The angioplasty or stent insertion had to have been performed percutaneously or though a limited groin incision. The treatment had to have been primary unless angioplasty failed and stenting was then performed as part of the primary procedure. We noted antiplatelet therapy preceding and following intervention. We did not consider drug-eluting balloons, stents and stent grafts.

We did not consider uncommon percutaneous interventions such as atherectomy. Secondary and primary assisted patency rates were only considered as aims in some trials, and we therefore did not include them.

Types of outcome measures

Primary outcomes
  • Rates of restenosis (in trials with at least six months follow-up and using techniques directly imaging the treatment site - duplex ultrasound and angiography).

Secondary outcomes
  • Clinical outcomes; improvement in ankle brachial index (ABI) or treadmill walking distance, and quality of life scores as assessed by the trialists.

Search methods for identification of studies

Electronic searches

For this update the Cochrane Peripheral Vascular Diseases (PVD) Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched August 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 6, part of The Cochrane Library (www.thecochranelibrary.com). See Appendix 1 for details of the search strategy used to search CENTRAL. The Specialised Register is maintained by the TSC and is constructed from weekly electronic searches of MEDLINE, EMBASE, CINAHL, AMED, and through handsearching relevant journals. The full list of the databases, journals and conference proceedings which have been searched, as well as the search strategies used are described in the Specialised Register section of the Cochrane Peripheral Vascular Diseases Group module in The Cochrane Library (www.thecochranelibrary.com).

Searching other resources

We examined bibliographies of papers found through the searches to identify further trials.

Data collection and analysis

Selection of studies

Two review authors (MC and CT) independently selected trials for inclusion in the review. These trials were sent to a third review author (ADM) who confirmed they were acceptable for inclusion. The section Criteria for considering studies for this review details the inclusion criteria used for the selection process.

Data extraction and management

Two review authors (MC and CT) collected data on each trial, including information on the participants (age and sex distribution, measures of severity of claudication such as walking distance, ABI), the interventions (angioplasty and stent type, control intervention, usual care in both groups) and the outcomes (as specified in Types of outcome measures). Data were independently extracted by MC and CT, and then cross-checked by ADM.

Assessment of risk of bias in included studies

Two review authors (MC and CT) assessed the methodological quality of each trial independently according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), resolving discrepancies by discussion.

Two review authors (MC and CT) examined six key domains of the Cochrane 'Risk of bias' tool. We assessed and classified these domains as being at either a low risk of bias or a high risk of bias. Where insufficient detail was reported in a study to assess the risk, we reported this as 'unclear'. In addition to the six key domains, we reported any other form of bias noted in the study.

Measures of treatment effect

We synthesised data by comparing group results. We did not combine individual data from different trials. We used Mantel-Haenszel odds ratios (ORs) and 95% confidence intervals (CIs) for dichotomous variables, and mean differences and 95% CIs for continuous variables.

Unit of analysis issues

For the primary outcome rates of restenosis the unit of analysis was the limb rather than the individual participant.

For the secondary outcomes ABI, walking distance and quality of life score the unit of analysis was the participant.

Dealing with missing data

All analyses were based on endpoint data from the individual clinical trials, which all quoted intention-to-treat results. We contacted individual trial authors for missing data where necessary.

Assessment of heterogeneity

We explored clinical heterogeneity in the studies using the previously identified characteristics of the studies and the quality of the included studies. We used the Chi² test to test for heterogeneity where data were pooled. A P value of < 0.10 was deemed to indicate heterogeneity.

Assessment of reporting biases

We tested for publication bias using the funnel plot for those meta-analyses where sufficient studies were included.

Data synthesis

The data analysis comprised a comparison of group results where feasible. Statistical analyses followed the standard methods of the Cochrane PVD Group. All analyses were based on endpoint data from the individual clinical trials, which all quoted intention-to-treat results.

We used a fixed-effect Mantel-Haenszel meta-analysis model, but a random-effects model for analyses showing significant heterogeneity (P < 0.10).

Subgroup analysis and investigation of heterogeneity

We had planned to stratify the data for severity of disease (claudication and critical limb ischaemia) but due to lack of available data we were unable to perform this analysis.

Sensitivity analysis

We did not perform any sensitivity analyses.

Results

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

Results of the search

See Figure 1.

Figure 1.

Study flow diagram.

Included studies

Summarised details of included studies can be found in the Characteristics of included studies table.

We included three new studies for this update (Dick 2009; RESILIENT; SUPER study), making a total of 11 randomised controlled trials (RCTs) which met the criteria for inclusion (Becquemin 2003; Cejna 2001; Dick 2009; Grenacher 2004; Grimm 2001; FAST Trial; RESILIENT; SUPER study; Vienna Absolute Trial; Vroegindeweij 1997; Zdanowski 1999). In all trials men and women with Fontaine stages II to IV were randomly allocated to percutaneous transluminal angioplasty (PTA) alone or to balloon angioplasty and stenting. Follow-up was reported up to 12 months (Becquemin 2003; Cejna 2001; Dick 2009; FAST Trial (see Krankenberg 2007); RESILIENT; SUPER study; Zdanowski 1999) and up to 24 months (Grenacher 2004; Grimm 2001; Vienna Absolute Trial (24 month data reported as Schillinger 2007 and Sabeti 2007); Vroegindeweij 1997). However, RESILIENT only reported 'freedom from target lesions revascularisation' and 'clinical success' at 24 and 36 months, so no new data could be added to any analysis from the three-year follow up data.

While PTA and stenting techniques were relatively consistent between trials, some trials used stainless steel stents (Becquemin 2003; Cejna 2001; Grenacher 2004; Grimm 2001; Vroegindeweij 1997) and some nitinol (Dick 2009; FAST Trial; RESILIENT; SUPER study; Vienna Absolute Trial; Zdanowski 1999).

Anticoagulation protocols varied extensively between trials, and in some cases even within trials (FAST Trial; Vienna Absolute Trial). No anticoagulant compliance checks were carried out.

There were no statistically significant differences in the major confounders (sex, age, smoking, dyslipidaemia (abnormal concentrations of lipids or lipoproteins in the blood), diabetes or hypertension) between the PTA and PTA with stent groups reported in any trial apart from Zdanowski 1999, where there was a slightly lower prevalence of men in the PTA-alone group.

Excluded studies

For this update we excluded one additional study (Brancaccio 2012).

Detailed reasons for trials being excluded can be found in the Characteristics of excluded studies table. In summary, the five studies were excluded for using drug-eluting stents (Duda 2006), covered stents (Saxon 2003),and for examining peripheral vascular disease that did not involve the superficial femoral artery (Ahn 1992). Brancaccio 2012 and the VascuCoil Trial were excluded because the outcomes reported were not relevant for this review.

Risk of bias in included studies

See Figure 2 and the risk of bias tables in Characteristics of included studies.

Figure 2.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Allocation

We deemed all the included studies to be at low risk of bias for random sequence generation and for allocation concealment.

Blinding

Blinding is not possible in this type of trial, so we deemed all the included studies to be at high risk of performance bias. We rated the studies at unclear risk of performance bias as radiological investigations for the primary outcome would show stent placement. According to the study publication, primary outcome assessment was blinded in Becquemin 2003, but it is unclear how this was achieved.

Incomplete outcome data

Attrition bias was low in all trials except for Grimm 2001, Vroegindeweij 1997 and Zdanowski 1999, where there was no statement on attrition or numbers.

Selective reporting

All but one (Zdanowski 1999) of the 11 included trials were deemed to be at low risk of reporting bias because all stated outcomes were accounted for. Zdanowski 1999 was deemed to be at unclear risk of bias because trial outcomes were not predefined.

Other potential sources of bias

Two trials were deemed to be at low risk of bias (Cejna 2001; Grenacher 2004).

Two trials (FAST Trial; Vienna Absolute Trial) quoted median values for treadmill distance and quality of life scores. These values were used as means for the purpose of analysis, with the standard deviation calculated from the interquartile range or confidence intervals assuming normal distribution of data. These data may have been skewed, and are therefore reported as medians.

Zdanowski 1999 did not specifically state inclusion and exclusion criteria for participants.

Three trials (FAST Trial; Grimm 2001; Vienna Absolute Trial) included participants with ipsilateral iliac artery stenoses, possibly biasing secondary outcomes such as quality of life data.

Becquemin 2003 reporting on drug prescription and salvage stenting in the PTA arm was unclear. Dick 2009 and FAST Trial did not report on adherence to medication protocol. Grimm 2001 did not assess medication, while RESILIENT did not have a medication compliance protocol. Vroegindeweij 1997 reported initial use of warfarin but medication protocol after that is unclear.

Effects of interventions

Primary outcomes

Rates of restenosis

At six months follow-up both primary duplex and angiographic patency were higher in the PTA plus stent group than the PTA alone group. The overall effect was significant (Figure 3; Mantel-Haenszel odds ratio (OR) 2.90, 95% confidence interval (CI) 1.17 to 7.18, Z = 2.31, P < 0.02, six trials, 578 participants), and Figure 4; OR 2.49, 95% CI 1.49 to 4.17, Z = 3.47, P = 0.0005, four trials, 329 participants for duplex and angiography respectively). This significant finding was only sustained at 12 months of follow-up (Figure 5) with regard to duplex patency with significant results with the inclusion of RESILIENT and the SUPER study (OR 1.78 95% CI 1.02 to 3.10, Z = 2.03, P < 0.04, nine trials, 858 participants). The significantly higher angiographic patency in the stent group at six months was lost by 12 months (five trials, 384 participants, Analysis 2.2; Figure 6). Twenty-four months follow up also showed no significant difference in duplex or angiographic patency (Analysis 3.1; Analysis 3.2).

Figure 3.

Forest plot of comparison: 1 Angioplasty versus stenting at 6 months, outcome: 1.1 Duplex patency.

Figure 4.

Forest plot of comparison: 1 Angioplasty versus stenting at 6 months, outcome: 1.2 Angiographic patency.

Figure 5.

Forest plot of comparison: 2 Angioplasty versus stenting at 12 months, outcome: 2.1 Duplex patency.

Figure 6.

Forest plot of comparison: 2 Angioplasty versus stenting at 12 months, outcome: 2.2 Angiographic patency.

For restenosis rates at 12 months we created a funnel plot to check for publication bias (Figure 7). The plot showed asymmetry, consistent with the significant heterogeneity seen in the analysis (Chi² test for heterogeneity P = 0.002).

Figure 7.

Funnel plot of comparison: 2 Angioplasty versus stenting at 12 months, outcome: 2.1 Duplex patency.

Secondary outcomes

Clinical outcomes
Ankle brachial index

Cejna 2001; Grimm 2001; Vroegindeweij 1997 reported significant improvement in ABI in both groups when compared to pre-intervention ABI, with no difference between groups immediately post-intervention. By 12 months there was no difference in ABI between the treatment groups (Analysis 2.3), even with the addition of the SUPER study in this updated review (OR 0.03, 95% CI -0.05 to 0.11, P = 0.49, four trials, 440 participants). There was significant heterogeneity between studies (Chi² test for heterogeneity P < 0.00001).

One study (Vienna Absolute Trial; 98 participants) reported ABI at 24 months showing no difference between the PTA and PTA plus stenting groups (Analysis 3.3).

Treadmill walking distance

At six months, only one study reports walking distance(Vienna Absolute Trial; 104 participants), which showed a benefit for stenting (Analysis 1.4). However the inclusion of the FAST Trial at 12 months, which was in favour of PTA alone, means that there was no overall difference between the treatment groups (two trials, 240 participants; random effects model; Analysis 2.4). There was significant heterogeneity as a result (Chi² test for heterogeneity P < 0.00001).

One study (Vienna Absolute Trial; 98 participants) reported treadmill walking distance at 24 months showing no difference between the PTA and PTA plus stenting groups (Analysis 3.3).

Quality of life scores

Quality of life data were only available for meta-analysis from one RCT (Vienna Absolute Trial). There was no significant difference at six or 12 months in either physical quality of life (P = 0.15 and P = 0.48 respectively) or mental quality of life (P = 0.49 and P = 0.21 respectively) between the two treatment groups (Analysis 1.5; Analysis 2.5). SUPER study reported results from EuroQol 5D questionnaires which could not be included in analysis. The authors of this study found no difference between the treatment groups. RESILIENT reported no difference in quality of life or walking distance QoL scores at any time interval between the angioplasty and stenting groups (P > 0.05 but not reported precisely).

Discussion

Summary of main results

The major finding of this analysis was that lesions of the superficial femoral artery treated by percutaneous transluminal angioplasty (PTA) with stent insertion show a small, statistically significant short-term improvement in primary patency over lesions treated with PTA alone (six trials, 578 participants). This effect is most prominent at six months and diminishes with time. A similar but smaller effect is seen for ankle brachial index (ABI) (one trial, 104 participants), while we observed a more pronounced improvement in treadmill walking distance in participants with PTA with stent insertion at six months (one trial, 104 participants), but not at 12 months (two trials, 240 participants) and 24 months (one trial, 98 participants). Quality of life, however, showed no significant difference between participants treated with PTA alone or PTA with stent insertion at any time interval. Intermittent claudication was the predominant symptom treated.

Overall completeness and applicability of evidence

Heterogeneity between trial outcomes means that while a large number of participants were available, overall some analyses contain small numbers of studies and therefore few participants. These analyses should be interpreted with caution. The Chi² test for heterogeneity for ABI was P < 0.00001 at 12 months, and was P < 0.00001 for treadmill walking distance at 12 months. In each case, the Vienna Absolute Trial reports higher values than the other studies, although the reasons for this are unclear. These results must therefore also be interpreted with caution. The Vienna Absolute Trial found strongly in favour of PTA and stenting and had a relatively large number of participants. This study therefore contributed a large weight towards analyses in which it was included, and is the main reason many forest plots show significance towards PTA and stenting. Nevertheless, the other large RCTs (Cejna 2001; FAST Trial) which showed no difference between groups were included in the primary outcome measure analyses: duplex and angiographic patency, with Vienna Absolute Trial. It is notable that at 12 months the inclusion of data from Becquemin 2003 produces a non-significant difference between PTA and PTA with stenting for angiographic patency. The finding in favour of stenting for primary duplex patency at 24 months does not include as many studies as at six and 12 months, and is so small that the inclusion of a small amount of data from another study could cause the overall difference to be statistically non-significant.

Although Grenacher 2004 reports primary duplex patency, the numbers of participants at each time interval is unclear. For this reason we could not include the results in the meta-analyses. The inclusion of these data would diminish the difference between PTA and PTA with stenting and may have made the 12-month difference non-significant. We did not include secondary and primary assisted patency rates as outcome measures due to the differences in reporting between trials.

No trial reported data in a way that allowed results to be separated by Rutherford/Fontaine stages or by chronic (claudicants) and critical ischaemia. This might have been useful, as differences between these groups may be present. No trial was powered in this way, so even if subgroup results were reported their validity would have been questionable.

Quality of the evidence

Six trials used nitinol stents (Dick 2009; FAST Trial; RESILIENT; SUPER study; Vienna Absolute Trial; Zdanowski 1999), while the other trials used stainless steel. There is speculation that nitinol stents may perform differently to stainless steel, although this is not apparent in these data. Indeed, two trials (FAST Trial; Vienna Absolute Trial) used nitinol stents with similar participant numbers and procedural protocols, but showed differing outcomes. The reasons for this are unclear, but one obvious difference between these trials was the antiplatelet therapy protocol used. In the Vienna Absolute Trial clopidogrel is used for long-term anticoagulation, whereas aspirin is used in both Cejna 2001 and FAST Trial. Additionally, Cejna 2001 excluded participants with ipsilateral iliac artery disease, whereas in the FAST Trial and the Vienna Absolute Trial the authors treated ipsilateral iliac disease with angioplasty and then included the participant in the trial. Medication is thus a major confounding factor between trials, especially the use of clopidogrel which is known to be associated with improved stent patency in coronary artery stents (Becker 2008).

Becquemin 2003 specifically states that 'bailout' stenting was performed in 15% of participants in the PTA-alone arm, and it is unclear whether these participants were included in the PTA arm for analysis at 12 months. The FAST Trial excluded PTA participants requiring a bailout stent. The fate of such participants in the other trials was unclear. This is another potential source of bias, as in Becquemin 2003 a significant difference may be present if the participants undergoing bailout stenting were subsequently included in the stent arm, or excluded from the trial. RESILIENT provided high participant numbers but cross-over to stent implantation in the angioplasty arm was high (40%), complicating data analysis.

Trials sponsored by device companies are statistically more likely to produce results in favour of the device (here stents) being tested (Lundh 2012; Djulbegovic 2013). This was true of many of the trials included in this analysis (Becquemin 2003; Cejna 2001; FAST Trial; Grenacher 2004; Grimm 2001; RESILIENT; SUPER study; Vienna Absolute Trial) and therefore may bias outcomes in favour of stents.

Reviewing the acceptability and quality of the evidence, it is therefore difficult to accept that the differences found between the PTA alone and PTA with stenting groups are of clinical relevance.

Potential biases in the review process

Two trials (Vienna Absolute Trial; FAST Trial) quoted medians for ABI which we converted to means for the benefit of the analysis in this review. Given only the median value and interquartile range, we used the reported median value as the mean value and calculated the standard deviation according to guidance described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Trials varied between using participants and limbs as their unit of analysis; however, we converted all data into limbs treated for analysis of the primary outcome patency rates. For the secondary outcomes we deemed the unit of analysis to be the participant.

Agreements and disagreements with other studies or reviews

Meta-analysis of stenting in femoropopliteal disease has become popular in the past five years. Four others exist (Acin 2012; Kasapis 2009; Mwipatayi 2008; Vardi 2014) as well as this review. Acin 2012 only analysed the nitinol stent trials included in our review. They found a trend in favour of stenting, but the total numbers in that analysis were just under half the total included in this review. Kasapis 2009 found no significant difference between treatment groups, and Vardi 2014 only examined one-month safety data in detail. An older analysis (Mwipatayi 2008) also found no difference between the treatment groups for primary or secondary patency.

Authors' conclusions

Implications for practice

The current trial data indicate that there is a small short-term patency benefit for percutaneous transluminal angioplasty (PTA) with stenting over PTA alone for treating lesions of the superficial femoral artery. However, the magnitude of the benefit is small and inconsistent. Protocols varied between trials, and the benefit may be limited to people with superficial femoral artery (SFA) disease subsequently treated with long-term clopidogrel. Haemodynamic findings are often used to assess the success of angioplasty and stent insertion. Importantly however, clinical findings, especially quality of life, is not significantly improved by this treatment strategy.

Many of these trials predominantly used claudicants for intervention. Current best evidence shows that exercise therapy is more useful than angioplasty for sustained improvements in quality of life and walking distance as the initial treatment of claudication (Frans 2012; Mazari 2012; Watson 2008). The National Institute for Health and Care Excellence (NICE) therefore recommends supervised exercise therapy as the first-line treatment (NICE 2012). In this context, measures of angiographic or duplex patency can be misleading, as they do not equate to the most important outcomes for the patient: walking distance and quality of life. Small improvements in short-term patency using stents are also expensive from a health economics point of view. The current evidence base does not support the use of routine stent insertion following PTA for treatment of lesions of the SFA.

Implications for research

A trial with quality of life, perceived and actual walking differences, and survival with intact limb would have more clinically useful endpoints than measures of primary patency.

The effect of antiplatelet therapy on PTA and stenting of SFA lesions needs to be properly investigated in a randomised controlled trial. Consideration should also be given to including a non-intervention control group and two-year outcomes in the evaluation of new SFA stents. As only subgroups of participants may benefit from stenting, trials should be of sufficient size to allow for heterogeneity in, for example, concurrent lesions (often a finding in clinical practice) and severity of disease, and should offer at least a two-year follow-up.

Data and analyses

Download statistical data

Comparison 1. Angioplasty versus stenting at 6 months
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Duplex patency6578Odds Ratio (M-H, Random, 95% CI)2.90 [1.17, 7.18]
2 Angiographic patency4329Odds Ratio (M-H, Fixed, 95% CI)2.49 [1.49, 4.17]
3 Ankle brachial index1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
4 Treadmill walking distance1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
5 Quality of life1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
5.1 Physical quality of life1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
5.2 Mental quality of life1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 1.1.

Comparison 1 Angioplasty versus stenting at 6 months, Outcome 1 Duplex patency.

Analysis 1.2.

Comparison 1 Angioplasty versus stenting at 6 months, Outcome 2 Angiographic patency.

Analysis 1.3.

Comparison 1 Angioplasty versus stenting at 6 months, Outcome 3 Ankle brachial index.

Analysis 1.4.

Comparison 1 Angioplasty versus stenting at 6 months, Outcome 4 Treadmill walking distance.

Analysis 1.5.

Comparison 1 Angioplasty versus stenting at 6 months, Outcome 5 Quality of life.

Comparison 2. Angioplasty versus stenting at 12 months
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Duplex patency9858Odds Ratio (M-H, Random, 95% CI)1.78 [1.02, 3.10]
2 Angiographic patency5384Odds Ratio (M-H, Fixed, 95% CI)1.30 [0.84, 2.00]
3 Ankle brachial index4441Mean Difference (IV, Random, 95% CI)0.03 [-0.05, 0.11]
4 Treadmill walking distance2240Mean Difference (IV, Random, 95% CI)41.72 [-102.34, 185.78]
5 Quality of life1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
5.1 Physical quality of life1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
5.2 Mental quality of life1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 2.1.

Comparison 2 Angioplasty versus stenting at 12 months, Outcome 1 Duplex patency.

Analysis 2.2.

Comparison 2 Angioplasty versus stenting at 12 months, Outcome 2 Angiographic patency.

Analysis 2.3.

Comparison 2 Angioplasty versus stenting at 12 months, Outcome 3 Ankle brachial index.

Analysis 2.4.

Comparison 2 Angioplasty versus stenting at 12 months, Outcome 4 Treadmill walking distance.

Analysis 2.5.

Comparison 2 Angioplasty versus stenting at 12 months, Outcome 5 Quality of life.

Comparison 3. Angioplasty versus stenting at 24 months
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Duplex patency3188Odds Ratio (M-H, Fixed, 95% CI)1.67 [0.91, 3.07]
2 Angiographic patency274Odds Ratio (M-H, Fixed, 95% CI)0.70 [0.28, 1.77]
3 Ankle brachial index1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
4 Treadmill walking distance1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
Analysis 3.1.

Comparison 3 Angioplasty versus stenting at 24 months, Outcome 1 Duplex patency.

Analysis 3.2.

Comparison 3 Angioplasty versus stenting at 24 months, Outcome 2 Angiographic patency.

Analysis 3.3.

Comparison 3 Angioplasty versus stenting at 24 months, Outcome 3 Ankle brachial index.

Analysis 3.4.

Comparison 3 Angioplasty versus stenting at 24 months, Outcome 4 Treadmill walking distance.

Appendices

Appendix 1. CENTRAL search strategy

#1MeSH descriptor: [Angioplasty] explode all trees4233
#2(angioplas* or percutan* or PTA)10083
#3recanali* or revascular*5220
#4dilat*6100
#5balloon6019
#6MeSH descriptor: [Endovascular Procedures] explode all trees5676
#7endovascular1369
#8#1 or #2 or #3 or #4 or #5 or #6 or #721661
#9MeSH descriptor: [Blood Vessel Prosthesis] explode all trees443
#10MeSH descriptor: [Blood Vessel Prosthesis Implantation] this term only489
#11MeSH descriptor: [Stents] explode all trees3102
#12*stent* or graft* or endograft* or endoprosthe*50066
#13powerlink 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 Luminex372
#14#9 or #10 or #11 or #12 or #1350439
#15MeSH descriptor: [Arteriosclerosis] this term only894
#16MeSH descriptor: [Arteriolosclerosis] this term only0
#17MeSH descriptor: [Arteriosclerosis Obliterans] this term only72
#18MeSH descriptor: [Atherosclerosis] this term only417
#19MeSH descriptor: [Arterial Occlusive Diseases] this term only770
#20MeSH descriptor: [Intermittent Claudication] this term only724
#21MeSH descriptor: [Peripheral Vascular Diseases] explode all trees2191
#22MeSH descriptor: [Vascular Diseases] this term only393
#23MeSH descriptor: [Leg] explode all trees and with qualifiers: [Blood supply - BS]1090
#24MeSH descriptor: [Femoral Artery] explode all trees736
#25femoro*541
#26(atherosclero* or arteriosclero* or PVD or PAOD or PAD)17611
#27(arter*) near (*occlus* or steno* or obstuct* or lesio* or block* or obliter*)4959
#28(vascular) near (*occlus* or steno* or obstuct* or lesio* or block* or obliter*)1413
#29(vein*) near (*occlus* or steno* or obstuct* or lesio* or block* or obliter*)744
#30(veno*) near (*occlus* or steno* or obstuct* or lesio* or block* or obliter*)1000
#31(peripher*) near (*occlus* or steno* or obstuct* or lesio* or block* or obliter*)1379
#32peripheral near/3 dis*3350
#33arteriopathic16
#34(claudic* or hinken*)1467
#35(isch* or CLI)17261
#36dysvascular*25
#37leg near/4 (obstruct* or occlus* or steno* or block* or obliter*)186
#38limb near/4 (obstruct* or occlus* or steno* or block* or obliter*)240
#39(lower near/3 extrem*) near/4 (obstruct* or occlus* or steno* or block* or obliter*)145
#40#15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38 or #3940689
#41#8 and #14 and #40 in Trials1852

What's new

DateEventDescription
1 August 2013New search has been performedSearches rerun. Three new studies included, one new study excluded and two ongoing studies identified.
1 August 2013New citation required but conclusions have not changedSeaches rerun. Three new studies included, one new study excluded and two ongoing studies identified. Risk of bias tables completed and review text updated. Conclusions not changed

History

Protocol first published: Issue 4, 2007
Review first published: Issue 2, 2009

DateEventDescription
29 May 2008AmendedConverted to new review format.

Contributions of authors

MMC selected trials, assessed the methodological quality of trials, extracted data and analysed results.
CPT selected trials, assessed the methodological quality of trials, extracted data and analysed results.
MMC and CPT ranked the allocation concealment of the trials and checked the completed manuscript.
ADM checked the selection of trials, cross checked data extraction and resolved any disagreements.

Declarations of interest

MMC: none known
ADM: I act as a consultant to LeMaitre vascular and have presented at their sales meetings. This is compliant with US legislation. LeMaitre vascular makes grafts for bypass surgery. The aortic intervention division of Cook Medical supported my attendance at the Veith meeting in November 2013 by paying for flights, accommodation and meeting fee. I am the examinations director and a member of the executive committee of UEMS Section and Board of Vascular Surgery. They have paid my travel expenses to committee meetings and to run the European Exam in vascular surgery (FEBVS).
CPT: none known

Sources of support

Internal sources

  • No sources of support supplied

External sources

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

    The PVD Group editorial base is supported by the Chief Scientist Office.

  • National Institute for Health Research (NIHR), UK.

    The PVD Group editorial base is supported by a programme grant from the NIHR.

Differences between protocol and review

We assessed clinical outcome as a secondary outcome to allow the assessment of ankle brachial index (ABI) and treadmill walking distance.

We could not stratify data for whether the interventions tested were performed for claudication or for critical limb ischaemia, as RCTs did not report individual data.

We assessed the methodological quality of the included studies using the 'Risk of bias' tool from The Cochrane Collaboration (Higgins 2011).

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Becquemin 2003

Methods

Study design: RCT

Method of randomisation: Concealed randomisation using computer software.

Blinding: Unblinded, intention-to-treat.

Exclusions post-randomisation: 24.

Losses to follow-up: 31 PTA, 32 Stent.

Cross-over to stenting in PTA group: 15.

Participants

Country: France.

Setting: Hospital.

No. of participants: 227 (227 limbs).

Age (mean): 66 years.

Gender: 142 men, 85 women.

Inclusion criteria: Inflow vessels free from significant lesion; single SFA lesion 1 cm from origin and 5 cm from proximal projection of knee joint; lesion length 1 cm - 7 cm; at least 1 patent leg artery.

Exclusion criteria: Acute ischaemia, previous surgery, haemorrhagic diathesis, hypercoagulation.

Interventions

PTA (115): over the wire.

Stent (112): Stainless steel 'Palmaz'.

Low molecular weight heparin for 24 hours, then aspirin or ticlopidine lifelong.

Outcomes

Pre-dischage duplex.

12 months: Angiography.

Primary patency defined as > 50% stenosis.

Notes

Salvage stenting used in the PTA arm in 15% of participants.

No doses for drugs. Aspirin or ticlopidine.

Sponsor: Cordis, Johnson & Johnson, Lafon, Aventis, and Société Française de Chirurgie Vasculaire.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer software used.
Allocation concealment (selection bias)Low riskPre-randomisation carried out using computer software by fax or telephone at least 24 hours before randomisation. During the operation, randomisation was made by telephone call.
Blinding of participants and personnel (performance bias)
All outcomes
High riskTrials of this type cannot be blinded
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated but radiological investigations would show stent placement. Becquemin 2003 reports that primary outcome assessment was blinded but it is unclear how this was achieved.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo major attrition.
Selective reporting (reporting bias)Low riskAll participants and outcomes accounted for.
Other biasUnclear riskUnclear drug prescription and salvage stenting in PTA arm.

Cejna 2001

Methods

Study design: RCT

Method of randomisation: Concealed randomisation using randomisation envelopes.

Blinding: Unblinded, intention-to-treat.

Exclusions post-randomisation: None.

Losses to follow-up: 13 PTA, 20 Stent.

Cross-over to stenting in PTA group: 10.

Participants

Country: Austria.

Setting: Hospital.

No. of participants: 141 (154 limbs).

Age (mean): 67 years.

Gender: 95 men, 59 women. (This number refers to the total number of limbs i.e. 154. The ratio of male/female participants was not quoted in the article)

Inclusion criteria: Up to 3 5-cm lesions in SFA; or proximal popliteal arteries; at least 1 patent runoff vessel.

Exclusion criteria: Patients with acute thromboembolism; previous vascular surgery in treated segments; untreated iliac and CFA disease.

Interventions

PTA (77): over the wire.

Stent (77): Stainless steel 'Palmaz'.

100 mg aspirin bolus and 1000 iu heparin intraoperative, IV heparin for 24 hours, 100 mg aspirin lifelong.

Outcomes

48 hours, 3, 6 and 12 months: ABI.

6 and 12 months: Angiography.

Primary patency defined as greater than 30% stenosis.

Notes

Many follow-ups not at prescribed intervals and different numbers of participants for each outcome.

Sponsor: Johnson & Johnson Interventional Systems.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskConcealed randomisation using randomisation envelopes.
Allocation concealment (selection bias)Low risk"Participating centres were given a number of closed envelopes."
Blinding of participants and personnel (performance bias)
All outcomes
High riskImpossible in this type of trial.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated but radiological investigations would show stent placement.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo major attrition.
Selective reporting (reporting bias)Low riskAll participants and outcomes accounted for.
Other biasLow riskGood medication protocol.

Dick 2009

Methods

Study design: RCT

Method of randomisation: concealed, computerised and in sealed envelopes

Blinding: Unblinded, intention-to-treat

Exclusions post randomisation: None.

Losses to follow-up: 3 PTA, 2 Stent.

Cross-over to stenting in PTA group: 7

Participants

Country: Austria.

Setting: Hospital.

No. of participants: 73 (73 limbs).

Age (mean): 69

Gender: 50 men, 23 women.

Inclusion criteria: clinical, severe intermittent claudication or critical limb ischaemia with rest pain or ulcers. Anatomic, > 50% stenosis or occlusion of the SFA with target lesion between 30 and 200 mm.

Exclusion criteria: acute limb ischaemia, previous stenting or bypass surgery of SFA, untreated inflow disease of ipsilateral pelvic arteries and known intolerances to medications/contrast.

Interventions

100 mg aspirin clopidogrel 75 mg, statin and antihypertensive

PTA: 34 over the wire

Stent: 39 nitinol stents

Outcomes

Restenosis rates - 6-month Angiography

Primary patency defined as > 50% stenosis

Notes

Salvage stenting used in the PTA arm in 7 participants

Sponsor: No statement.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated random digits and sealed envelopes.
Allocation concealment (selection bias)Low riskComputer-generated random digits and sealed envelopes.
Blinding of participants and personnel (performance bias)
All outcomes
High riskImpossible in this type of trial.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated but radiological investigations would show stent placement.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo major attrition.
Selective reporting (reporting bias)Low riskAll outcomes accounted for.
Other biasUnclear riskNo statement on adherence to medication protocol.

FAST Trial

Methods

Study design: RCT

Method of randomisation: Concealed randomisation using randomisation envelopes provided by an independent data management organisation.

Blinding: Unblinded, intention-to-treat.

Exclusions post-randomisation: None.

Losses to follow-up: 6 PTA, 9 stent.

Cross-over to stenting in PTA group: 13.

Participants

Country: Germany.

Setting: Hospital.

No. of participants: 244 (244 limbs).

Age (mean): 66.5 years.

Gender: 168 men, 76 women.

Inclusion criteria: SFA lesion at least 1 cm from SFA origin and 1cm - 10 cm long; target lesion diameter at least 70% by visual estimate; all distal vessels patent; at least Rutherford 2 chronic limb ischaemia.

Exclusion criteria: Target lesion requiring pretreatment such as debulking; target lesion extending into popliteal artery; previous stent in target SFA; multiple lesions exceeding 10 cm; acute or subacute (≤ 4 weeks) thrombotic occlusion; an untreated ipsilateral iliac artery stenosis; ongoing dialysis and treatment with oral anticoagulation other than antiplatelet therapy.

Interventions

PTA (121): over the wire.

Stent (123): Nitinol.

100 mg aspirin for at least 10 days or 500 mg bolus preoperative. 3000 - 5000 iu heparin intraoperatively

Outcomes

1, 6 and 12 month follow-up: ABI, treadmill test, duplex ultrasound.

12-month biplane radiographs for participants receiving stent (detection of fractures).

Primary patency defined as proximal peak velocity ratio ≥ 2.4 on duplex ultrasound.

Notes

Participants with ipsilateral iliac artery stenosis underwent angioplasty and were not excluded.

Total occlusion rate difference (25% in PTA participants, 37% stent participant) may bias restenosis results (acknowledged).

Gender difference in restenosis rates in PTA arm only (acknowledged).

Compliance with aspirin/clopidogrel not assessed.

Reassessment blinding not stated.

Sponsor: C.R. Bard Inc.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomisation envelopes.
Allocation concealment (selection bias)Low risk4-block randomisation envelopes from independent data management company.
Blinding of participants and personnel (performance bias)
All outcomes
High riskImpossible in this type of trial.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated but radiological investigations would show stent placement.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo major attrition.
Selective reporting (reporting bias)Low riskAll outcomes accounted for.
Other biasHigh riskNo statement of adherence to medication protocol. Medians quoted and participants with ipsilateral iliac artery stenosis underwent angioplasty but were not excluded.

Grenacher 2004

Methods

Study design: RCT

Method of randomisation: Concealed randomisation using sealed randomisation envelopes.

Blinding: Unblinded, intention-to-treat.

Exclusions post-randomisation: None.

Losses to follow-up: 30.

Cross-over to stenting in PTA group: 1.

Participants

Country: Germany.

Setting: Hospital.

No. of participants: 116 (124 limbs).

Age (mean): 67 years.

Gender: 78 men, 38 women.

Inclusion criteria: Intermittent claudication or chronic limb ischaemia, lesion < 5 cm, at least 1 patent runoff vessel.

Exclusion criteria: Lesions greater than 5 cm in length requiring more than 2 stents; multifocal disease or complete obstruction in the SFA; haemodynamically relevant stenoses in the lower limb previously untreated; occlusion of more than 2 runoff vessels; existing contraindications for vascular surgery or anticoagulation.

Interventions

PTA (53): over the wire.

Stent (71): Stainless steel 'Palmaz'.

100 mg aspirin bolus and 5000 iu heparin intraoperative. Low molecular weight heparin for 48 hours, 100 mg aspirin lifelong.

Outcomes

3, 6, 12 and 24 month follow-up: Angiography and duplex ultrasound.

Primary patency defined as greater than 30% stenosis.

Notes

Numbers of participants undergoing duplex unclear and therefore not included in analysis.

Sponsor: No statement.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomisation envelopes.
Allocation concealment (selection bias)Low risk"The envelopes were opened after all inclusion and exclusion criteria were examined."
Blinding of participants and personnel (performance bias)
All outcomes
High riskImpossible in this type of trial.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated but radiological investigations would show stent placement.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo major attrition.
Selective reporting (reporting bias)Low riskAll outcomes accounted for.
Other biasLow riskGood medication and post-trial protocol.

Grimm 2001

Methods

Study design: RCT

Method of randomisation: Concealed randomisation using randomisation envelopes.

Blinding: Unblinded, intention-to-treat.

Exclusions post-randomisation: None.

Losses to follow-up: 12.

Cross-over to stenting in PTA group: none.

Participants

Country: Germany.

Setting: Hospital.

No. of participants: 53 (53 limbs).

Age (mean): 69 years.

Gender: 32 men, 21 women.

Inclusion criteria: SFA lesion at least 1 cm from SFA origin (including proximal popliteal artery); stenosis no longer than 5 cm; target lesion diameter at least 70% by visual estimate; vessel diameter between 4 mm and 8 mm.

Exclusion criteria: Lesions > 5 cm in length requiring more than 2 stents; multifocal disease or complete obstruction in the SFA; haemodynamically relevant stenoses in the lower limb previously untreated; occlusion of more than 2 runoff vessels; thrombus within the SFA; existing contraindications for vascular surgery or anticoagulation.

Interventions

PTA (23): over the wire.

Stent (30): Stainless steel 'Palmaz'.

1000 mg aspirin bolus and 5000 iu heparin intraoperative. IV heparin for 24 hours, 100 mg aspirin lifelong.

Outcomes

3, 6, 12 and 24 month follow-up: ABI, treadmill test, duplex ultrasound.

6-month angiography.

Primary patency defined as vessels without 1.5 greater systolic flow than in normal parts of the artery or angiographic reocclusion.

Notes

Participants with ipsilateral iliac or distal popliteal stenosis underwent angioplasty and were not excluded.

No clear mention of distal vessel patency. Primary patency definition for angiography unclear.

Aspirin compliance not assessed.

Sponsor: Johnson & Johnson Interventional Systems.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomisation envelopes.
Allocation concealment (selection bias)Low riskAdequate concealed randomisation using randomisation envelopes.
Blinding of participants and personnel (performance bias)
All outcomes
High riskImpossible in this type of trial.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated but radiological investigations would show stent placement.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo statement on attrition.
Selective reporting (reporting bias)Low riskAll outcomes accounted for.
Other biasUnclear riskMedication not assessed. Participants with ipsilateral iliac or distal popliteal stenosis underwent angioplasty and were not excluded.

RESILIENT

Methods

Study design: RCT

Method of randomisation: Concealed randomisation (computer-generated)

Blinding: Unblinded, intention-to-treat.

Exclusions post-randomisation: None.

Losses to follow-up: PTA 13, 22 Stent.

Cross-over to stenting in PTA group: 29

Participants

Country: USA (California) and Europe (Austria) - 24 centres.

Setting: Hospital.

No. of participants: 206 (206 limbs).

Age (mean): 67 years.

Gender: 143 men, 63 women.

Inclusion criteria: symptoms of intermittent claudication (Rutherford categories 1 - 3), candidates for angioplasty or stenting, de novo stenotic, occlusive, or restenotic lesions in SFA

Exclusion criteria: critical limb ischaemia (Rutherford categories 4 - 6), sensitivity to contrast media, renal and/or hepatic failure.

Interventions

81 mg aspirin (continue for 6 months), 75 mg clopidogrel (12 weeks post-procedure). Unfractionated heparin intra-procedure.

PTA (72): over the wire.

Stent (134): LifeStent nitinol self-expanding stent.

Outcomes

Freedom from target lesion revascularisation 6, 12 months.

Primary patency, duplex, 6 and 12 months.

QoL measures 6, 12 months (Short Form 8 Question Health Survey), walking distance score 6, 12 months (Walking Impairment Questionnaire).

Notes

Of 72 participants in angioplasty group, 29 underwent secondary bailout stenting procedure (due to inadequate PTA result, flow-limiting dissection or a residual stenosis).

Sponsor: Bard Peripheral Vascular.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated randomisation.
Allocation concealment (selection bias)Low riskComputer-generated randomisation.
Blinding of participants and personnel (performance bias)
All outcomes
High riskImpossible in this type of trial.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated but radiological investigations would show stent placement.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo major attrition.
Selective reporting (reporting bias)Low riskAll outcomes accounted for.
Other biasUnclear riskNo medication compliance protocol.

SUPER study

Methods

Study design: RCT

Method of randomisation: Concealed randomisation (computer-generated)

Blinding: Unblinded, intention-to-treat.

Exclusions post-randomisation: None.

Losses to follow-up: Not stated.

Cross-over to stenting in PTA group: 4, cross-over to PTA in stenting group: 4

Participants

Country: UK, 17 centres.

Setting: Hospital.

No. of participants: 150 (150 limbs).

Age (mean): 67 years.

Gender: 123 men, 27 women.

Inclusion criteria: symptoms of intermittent claudication (Rutherford categories 1 - 5), candidates for angioplasty or stenting, de novo stenotic, occlusive, or restenotic lesions in SFA.

Exclusion criteria: critical limb ischaemia (Rutherford 6), sensitivity to contrast media, renal and/or hepatic failure.

Interventions

PTA 76.
Stent 74. Nitinol.

3000 - 5000 iu heparin intra-procedure. Unclear antiplatelet as only 'recommended'.

Outcomes

Primary patency, duplex, baseline to 12 months.

QoL measures: EuroQol (EQ)-5D.

Notes

No strict antiplatelet protocol.

Sponsor: Cordis, Johnson & Johnson Medical Ltd.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated randomisation.
Allocation concealment (selection bias)Low riskComputer-generated randomisation.
Blinding of participants and personnel (performance bias)
All outcomes
High riskImpossible in this type of trial.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskRadiological investigations would show stent placement.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo major attrition.
Selective reporting (reporting bias)Low riskAll outcomes accounted for.
Other biasUnclear riskNo strict antiplatelet protocol.

Vienna Absolute Trial

Methods

Study design: RCT

Method of randomisation: Concealed randomisation using computer-generated randomisation envelopes.

Blinding: Unblinded, intention-to-treat.

Exclusions post-randomisation: None.

Losses to follow-up: None at 6 months, 3 at 12 months, 6 at 2 years.

Cross-over to stenting in PTA group: 17.

Participants

Country: Austria.

Setting: Hospital.

No. of participants: 104 (104 limbs).

Age (mean): 66.5 years.

Gender: 55 men, 49 women.

Inclusion criteria: SFA target lesion > 3 cm long; target lesion diameter at least 50% by visual estimate; at least 1 patent (< 50% stenosed) tibioperoneal runoff vessel; at least Rutherford 3 chronic limb ischaemia.

Exclusion criteria: Untreated inflow disease of ipsilateral pelvic arteries (> 50% stenosis or occlusion); previous bypass procedure or stent in target SFA; multiple lesions > 10 cm; acute critical limb ischaemia; an untreated ipsilateral iliac artery stenosis; known intolerance to study medications or contrast agents.

Interventions

PTA (53): over the wire.

Stent (51): Nitinol.

75 mg clopidogrel for at least 2 days or 300 mg bolus preoperative.

Outcomes

6 months: Rate of restenosis by angiography.

3, 6 and 12 months: Rate of restenosis (at least 50% luminal diameter) by duplex; occurrence of stent fractures; ABI; treadmill test; QoL (SF-36 questionnaire, Sabeti 2007).

6 and 12 months: Limb amputation or death.

Primary patency defined as > 50% stenosis.

24 months (Schillinger 2007): Rate of restenosis (at least 50% luminal diameter) by duplex; occurrence of stent fractures; ABI; treadmill test; re-intervention.

QoL measures: Short form 36

Notes

Full results published over 3 papers: Schillinger 2006; Schillinger 2007; Sabeti 2007. 2-year follow-up published for same cohort as Schillinger 2007 (clinical outcomes) and Sabeti 2007 (quality of life).

Uses medians for treadmill distance and QoL indicators.

Compliance with clopidogrel not assessed.

Sponsor: Guidant Endovascular Solutions.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated.
Allocation concealment (selection bias)Low riskConcealed randomisation using computer-generated randomisation envelopes.
Blinding of participants and personnel (performance bias)
All outcomes
High riskImpossible in this type of trial.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated but radiological investigations would show stent placement.
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo major attrition.
Selective reporting (reporting bias)Low riskAll outcomes accounted for.
Other biasUnclear riskMedians quoted for treadmill distances and QoL; these results may therefore be skewed.

Vroegindeweij 1997

Methods

Study design: RCT

Method of randomisation: Concealed randomisation using sealed randomisation envelopes.

Blinding: Unblinded, intention-to-treat.

Exclusions post-randomisation: None.

Losses to follow-up: None.

Cross-over to stenting in PTA group: 4.

Participants

Country: The Netherlands.

Setting: Hospital.

No. of participants: 51 (51 limbs).

Age (mean): 64.5 years.

Gender: 36 men, 15 women.

Inclusion criteria: Lesions confined to femoropopliteal artery.

Exclusion criteria: Below-knee popliteal disease; multisegmental disease; disease > 5 cm in length.

Interventions

PTA (27): over the wire.

Stent (24): stainless steel 'Palmaz'.
5000 iu heparin intraoperative. 3 months warfarin.

Outcomes

6 weeks, 3, 6, 9, 12, 18 and 24 month follow-up: ABI, treadmill test, duplex ultrasound.

Primary patency defined as proximal peak velocity ratio > 2.5 on duplex ultrasound.

Notes

Runoff vessel patency at time of intervention unclear. Participants with coexisting ipsilateral proximal arterial stenosis included.

Sponsor: No statement.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskConcealed randomisation using sealed randomisation envelopes.
Allocation concealment (selection bias)Low riskConcealed randomisation using sealed randomisation envelopes.
Blinding of participants and personnel (performance bias)
All outcomes
High riskImpossible in this type of trial.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated but radiological investigations would show stent placement.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo statement on attrition.
Selective reporting (reporting bias)Low riskAll outcomes accounted for.
Other biasUnclear riskWarfarin used initially then unclear medication protocol.

Zdanowski 1999

  1. a

    ABI: ankle brachial index
    CFA: common femoral artery
    iu: international units
    IV: intravenous
    PTA: percutaneous transluminal angioplasty
    QoL: quality of life
    RCT: randomised controlled trial
    SFA: superficial femoral artery

Methods

Study design: RCT

Method of randomisation: Computerised randomisation.

Blinding: Unblinded, intention-to-treat.

Exclusions post-randomisation: None.

Losses to follow-up: 1. 4 (2 in each group) subsequently underwent surgery within the trial time period. 7 refused angiography during follow-up.

Cross-over to stenting in PTA group: none.

Participants

Country: Sweden.

Setting: Hospital.

No. of participants: 32 (32 limbs).

Age (mean): 71 years.

Gender: 14 men, 18 women.

Inclusion criteria: Lesions confined to femoropopliteal artery.

Exclusion criteria: Unclear.

Interventions

PTA (27): over the wire.

Stent (24): nitinol 'Strecker'.
160 mg aspirin post-operative.

Outcomes

1 year: ABI, angiography.

Primary patency defined as > 50% stenosis.

Notes

Unclear inclusion/exclusion criteria.

Poor anticoagulation.

Sponsor: No statement.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputerised randomisation.
Allocation concealment (selection bias)Low riskComputerised randomisation.
Blinding of participants and personnel (performance bias)
All outcomes
High riskImpossible in this type of trial.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated but radiological investigations would show stent placement.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo statement or participant numbers for attrition.
Selective reporting (reporting bias)Unclear riskIll-defined outcomes at trial conception
Other biasUnclear riskUnclear inclusion and exclusion criteria for participants.

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
  1. a

    ePTFE: expanded polytetrafluoroethylene
    PTA: percutaneous transluminal angioplasty
    SFA: superficial femoral artery

Ahn 1992Only a description of the proposal for setting up randomised controlled trial to investigate SFA disease.
Brancaccio 2012Randomised controlled trial which had the relevant comparisons but not outcomes.
Duda 2006Randomised controlled trial comparing bare metal stent with drug-eluting stent; no PTA-only arm.
Saxon 2003Randomised controlled trial comparing PTA with PTA plus ePTFE stent graft rather than stent.
VascuCoil TrialRandomised controlled trial designed to enrol 500 participants with stenotic or occluded SFA disease. The trial was stopped early due to slow participant enrolment. Participants (266) were randomised to PTA versus PTA plus stent (Intracoil). Greenberg 2004 reports cost, resource utilisation and in-hospital complications, outcomes not relevant for this review.

Characteristics of ongoing studies [ordered by study ID]

NCT01183117

Trial name or titleA clinical investigation of SM-01 stenting versus PTA for the treatment of superficial femoral artery disease
MethodsRandomised controlled trial
Participants

Men or women 20 years or older.

Inclusion criteria:

Symptomatic leg ischaemia by Rutherford Classification (category 1, 2, or 3).

Lesion length ≥ 40 mm to ≤ 150 mm (must be treatable with no more than 2 SM-01 stents. Overlap should be about 1 cm if 2 stents are used)

Reference vessel diameter (RVD) ≥ 4.0 mm and ≤ 7.0 mm.

All lesions are to be located ≥ 3.0 cm proximal to the superior edge of the patella, and ≥ 1.0 cm distal to the SFA/PFA bifurcation.

≥ 50% stenosis or total occlusion.

Patent infrapopliteal and popliteal arteries, i.e., single-vessel runoff or better with at least 1 of 3 vessels patent (< 50% stenosis) to the ankle or foot.

Interventions

Device: SM-01
SM-01 is a self-expandable, crush recoverable stent with a diameter larger than that of the arterial lumen. The stent is indicated for use in a vessel with a diameter 1 - 2 mm smaller than the nominal stent diameter. This stent will open to the diameter of the artery and will continue to apply expanding force on the artery.

Active comparator: PTA balloon angioplasty.

OutcomesPrimary outcome measures: Non-TVF (Target vessel failure) rate (time frame: 12 months). The primary endpoint will be freedom from TVF defined as any events of clinical driven (confirmed by duplex ultrasound or angiography) TLR/TVR, procedure failure, amputation of the target lesion's leg, procedure- or device-related death, occlusion of target lesion, or > 70% restenosis of target lesion.
Starting dateJuly 2010
Contact informationTakuro Takagi, MD
Notes 

Osprey

Trial name or titleOSPREY. Occlusive/Stenotic Peripheral artery Revascularization Study
MethodsJP arm: randomised trial comparing PTA with stenting
ParticipantsSFA disease Rutherford classification 2,3 or 4
InterventionsPTA versus stenting
OutcomesBailout stenting, procedure failure, death, amputation
Starting date2009
Contact informationHiroyoshi Yokoi, Kokura Memorial Hospital, Kitakyusyu, Japan
Notes 

Ancillary