Covered vs Uncovered Stents for Aortoiliac and Femoropopliteal Arterial Disease

Abstract

Purpose: To evaluate outcomes of covered vs bare metal stents for the treatment of lower limb peripheral artery disease. Methods: A search of electronic databases was performed to identify all studies comparing outcomes of covered vs bare metal stents for treatment of aortoiliac and femoropopliteal arterial disease. The Cochrane tool and the Newcastle-Ottawa scale were used to assess the risk of bias in randomized controlled trials (RCTs) and observational studies, respectively. Fixed or random effects models were applied to analyze pooled outcome data. The results for dichotomous outcome variables are presented as the odds ratio (OR) and 95% confidence interval (CI); intergroup comparisons of continuous clinical variables are reported as the mean difference (MD) and 95% CI. Results: Two RCTs and 4 retrospective cohort studies, enrolling 744 patients (mean age 67 years; 477 men) and 918 diseased arteries, were identified. For aortoiliac disease, treatment with a covered stent showed no significant improvement in primary patency (OR 2.10, 95% CI 0.48 to 9.11, p=0.32), but it was associated with higher ankle-brachial index (ABI) (MD 0.08, 95% CI 0.07 to 0.09, p<0.001) and a lower reintervention rate (OR 0.19, 95% CI 0.09 to 0.42, p<0.001). For femoropopliteal disease, use of covered stents was associated with increased primary patency (OR 1.84, 95% CI 1.11 to 3.06, p=0.02), higher ABI (MD 0.08, 95% CI 0.00 to 0.16, p=0.04), and a lower reintervention rate (OR 0.51, 95% CI 0.30 to 0.87, p=0.01). No significant differences in technical success, complications, limb salvage, or survival were identified between the groups in either segment. Conclusion: Theoretically, the use of covered stents may increase the patency rate due to decreased restenosis after stent placement. This analysis found that the primary patency was improved with the use of a covered stent in femoropopliteal lesions but not in aortoiliac disease. Improved outcomes were seen with covered stents compared with bare metal stents as indicated by a lower need for reintervention and an improved ABI. It remains to be investigated whether such beneficial effects can be translated into improved clinical outcomes, such as limb salvage and amputation-free survival. Long-term results of the comparative efficacy of covered stents over bare metal stents are not currently available.

Keywords

aortoiliac segment bare metal stent covered stent-graft endovascular treatment/therapy femoropopliteal segment peripheral artery disease

Introduction

Advances in technology in the past decade have conspicuously altered revascularization strategies from traditional open surgical approaches toward percutaneous endovascular treatments.¹ Endovascular therapy is associated with advantages over open surgical revascularization, such as lower morbidity and mortality.^2,3 The availability of stents has made catheter-based percutaneous revascularization procedures of the lower extremities more durable and predictable.¹

Bare metal stents (BMS) are associated with improved long-term patency compared with balloon angioplasty alone⁴; however, they do not prevent neointimal hyperplasia, and the risk for in-stent restenosis remains significant.⁵ An expanded polytetrafluoroethylene (ePTFE) covering of stents allows exclusion of injured atheromatous plaque and prevents ingrowth of neointimal tissue. Therefore, theoretically, the use of ePTFE-covered stents may increase the patency rate due to decreased restenosis after stent placement. Although the results of numerous reports are promising, the outcomes of covered stents vs BMS for treatment of lower limb peripheral artery disease (PAD) are not known.

Our objective was to perform a systematic review of the literature and conduct a meta-analysis of outcomes of covered stents vs BMS for the treatment of aortoiliac and femoropopliteal disease. The robustness and quality of the available evidence was evaluated in a systematic and explicit approach with consideration for consistency and generalizability of the results.

Methods

Study Design and Eligibility Criteria

This systematic review was conducted and presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards.⁶ The protocol for the review specified the evaluation of all randomized controlled trials (RCTs) and observational studies investigating outcomes of covered stents vs BMS for the treatment of aortoiliac and femoropopliteal disease. The use of the ePTFE-covered stent was considered the intervention of interest and the BMS was the comparator.

Primary patency was the main outcome measure; secondary outcome measures included secondary patency, technical success, need for reintervention, limb salvage, survival, major complications, and ankle-brachial index (ABI). Primary patency was defined as uninterrupted patency of the stent with no procedure performed on the stent or the adjacent native vessel.⁷ Secondary patency referred to patency restored by thrombectomy, thrombolysis, or transluminal angioplasty after stent occlusion.⁷ Technical success was defined as successful implantation of the stent(s) with <30% residual stenosis within the target lesion.

Literature Search Strategy

Two authors (S.H. and S.H.) independently searched the following electronic databases: MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL). The last search was run on 29 November 2015. The details of the search strategy, which was adapted according to thesaurus headings, search operators, and limits in each of the above databases, are delineated in the Appendix. In addition, the following trial databases were searched for details of ongoing and unpublished studies: World Health Organization International Clinical Trials Registry (http://apps.who.int/trialsearch/), ClinicalTrials.gov (http://clinicaltrials.gov/), and the ISRCTN Register (http://www.isrctn.com/). The bibliographies of relevant articles and reviews were searched for further potentially eligible trials. Moreover, leading journals in vascular and endovascular surgery were searched manually: Journal of Vascular Surgery, European Journal of Vascular and Endovascular Surgery, and Journal of Endovascular Therapy. No language restrictions were applied.

Study Selection

The same 2 authors independently assessed the title and abstract of articles identified from the literature searches. The full texts of relevant reports were retrieved and those articles that met the eligibility criteria were selected. Any discrepancies in study selection were resolved by discussion between the authors. An independent third author (S.A.A.) was consulted in the event of disagreement. The searches identified 357 articles, of which 6 articles^8–13 were eligible for analysis (Figure 1). These included 2 RCTs^10,11 and 4 retrospective cohort studies^8,9,12,13 enrolling a total of 744 patients with 918 diseased arteries. Four studies^8,9,11,12 included 469 patients (mean age 66 years; 283 men) with aortoiliac or iliac occlusive disease, and 2 studies^10,13 comprised 275 patients (mean age 70 years; 194 men) with femoropopliteal occlusive disease. The characteristics of the included studies are presented in Table 1.

Table 1.

Characteristics of the Included Studies.

Author	Country	Type of Study	Clinical Presentation	Intervention	Control	Follow-up, mo
Piazza 2015	Italy	Retrospective cohort	Severe iliac artery obstructive lesions	ePTFE covered stent	Bare metal stent	20 (mean)
Humphries 2014	USA	Retrospective cohort	Aortoiliac occlusive disease	ePTFE covered BE stent	Bare metal BE stent	22 (mean)
Lammer 2013	Austria	Single blind multicenter (n=7) RCT	Symptomatic long femoropopliteal arteriosclerotic stenosis or occlusion	Heparin-bonded ePTFE covered stent	Bare metal stent	12
Vartanian 2013	USA	Retrospective cohort	Femoropopliteal occlusive disease	SE stent-graft	Bare metal SE stent	24.6 (median)
Mwipatayi 2011	Australia	Multicenter (n=8) RCT	Aortoiliac occlusive disease	ePTFE covered BE stent	Bare metal BE stent	18
Sabri 2010	USA	Retrospective cohort	Atherosclerotic occlusive disease at the aortic bifurcation	ePTFE covered kissing stent	Bare metal BE stent	21 (median)

Abbreviations: BE, balloon-expandable; ePTFE: expanded polytetrafluoroethylene; RCT, randomized controlled trial; SE, self-expanding.

Data Collection

An electronic data extraction spreadsheet was created in line with the Cochrane data collection form for intervention reviews; the spreadsheet was tested in randomly selected articles and adjusted accordingly. Data extraction included (1) study-related data (first author, year of publication, country of origin of the corresponding author, journal in which the study was published, study design, study size, and clinical condition of the study participants); (2) baseline demographic and clinical information (age, gender, diabetes mellitus, coronary heart disease, hypertension, hyperlipidemia, and smoking status); and (3) primary and secondary outcome data. Two authors (S.H. and S.H.) independently collected and recorded data and resolved disagreements by discussion. If no agreement could be reached, a third author (S.A.A.) was consulted.

Methodological Quality and Bias Assessment

The methodological quality and risk of bias of the included articles were assessed independently by 2 authors (S.H. and S.H.) using the Cochrane tool¹⁴ and the Newcastle-Ottawa scale (NOS)¹⁵ for assessing the risk of bias of randomized trials and observational studies, respectively. The Cochrane tool assesses domains including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other sources of bias, and for each individual domain classifies studies into low, unclear, and high risk of bias. The NOS uses a star system with a maximum of 9 stars to evaluate a study in 3 domains (8 items): the selection of the study groups, the comparability of the groups, and the ascertainment of the outcome of interest. For each item of the scale, each study was judged as low risk (1 star awarded) or high risk (no star awarded). Studies that received a score of 9 stars had a low risk of bias, studies that scored 7 or 8 stars were moderate risk, and those that scored ≤6 were high risk of bias. Disagreements were resolved by discussion between the reviewers. If no agreement could be reached, a third author (G.A.A.) acted as an adjudicator. A risk of bias graph was constructed to present the results.

Data Synthesis and Statistical Analyses

For dichotomous outcome variables (primary patency, secondary patency, technical success, need for reintervention, limb salvage, survival, and major complications), the odds ratio (OR) or, when the OR was not estimable, the risk difference (RD) was calculated as the summary measure and presented with the 95% confidence interval (CI). The OR is the odds of an event in the covered stent group compared to the BMS group. The RD is the difference in risk of an event in the covered stent group compared to the BMS group. For primary patency, secondary patency, limb salvage, and survival, an OR >1 would favor the covered stent. For major complications or need for reintervention, an OR <1 would favor the covered stent. For continuous parameters (ABI), the mean difference (MD) between the groups was calculated.

Depending on outcome parameters, the individual patient or individual diseased artery was the unit of analysis. Information about dropouts, withdrawals, and other missing data were recorded; if not reported, the study authors were contacted where possible. The final analysis was based on intention-to-treat data from the individual clinical studies. The Review Manager software (version 5.3; Cochrane Information Management System; http://ims.cochrane.org/revman ) was used for data synthesis.¹⁴ Extracted data were entered into Review Manager by the first independent author (S.H.) and checked by the second independent author (S.H.). Random or fixed effects modeling was used as appropriate for analysis; random effects models were used if considerable heterogeneity was found among the studies, as defined by Higgins and Altman.¹⁴ The results are reported in forest plots with 95% CI.

Heterogeneity among the studies was assessed using the Cochran Q test. Inconsistency was quantified by calculating I² and interpreted as follows: 0% to 40% might not be important, 30% to 60% may represent moderate heterogeneity, 50% to 90% may represent substantial heterogeneity, and 75% to 100% may represent considerable heterogeneity.¹⁴ The Egger regression intercept was used to formally assess reporting bias using the Comprehensive Meta-Analysis software (Biostat, Englewood, NJ, USA).

Sensitivity and Subgroup Analyses

Additional analyses were performed to explore potential sources of heterogeneity and assess the robustness of results. For each outcome, the primary analysis was repeated using random effects and fixed effect models. In addition, both the pooled OR and RD for each dichotomous variable were calculated. The effect of each study on the overall effect size and heterogeneity was assessed by repeating the analysis after removing one study at a time. Also, separate analyses were performed for studies with low, moderate, or high risk of bias to assess the change in direction of the effect size. Subgroup analyses were performed for RCTs.

Results

Aortoiliac Disease

Overall, 255 diseased arteries in 182 patients (mean age 65 years; 121 men) were treated with covered stents and 388 diseased arteries in 287 patients (mean age 66 years; 162 men) with BMS. The proportion of male patients was higher in the covered stent group (p=0.033). There was no significant difference between the groups in terms of age and comorbidities, such as hypertension (p=0.907), diabetes (p= 0.236), coronary heart disease (p=0.973), hyperlipidemia (p=0.487), or smoking (p=0.658). In terms of lesion characteristics, the proportions of TransAtlantic Inter-Society Consensus (TASC) II A and B lesions were significantly higher in the BMS group (p=0.008 and p=0.049, respectively). There was no significant difference in the proportions of TASC II C lesions (p=0.793), but the proportion of TASC II D lesions was significantly higher in the covered stent group (p<0.001). The baseline demographics of the population with aortoiliac disease are presented in Table 2.

Table 2.

Baseline Demographics of the Included Population With Aortoiliac Disease.^a

	Stent Type	Authors				Overall	p^b
	Stent Type	Piazza 2015	Humphries 2014	Mwipatayi 2011	Sabri 2010	Overall	p^b
Age, y	Covered	70.1±9.4	64±11	65.34±1	61±10.2	—
Age, y	BMS	70.1±11	65±11	67.2±1.3	61.5±12.8	—
Men	Covered	43/57	19/37	42/62	17/26	121/182 (66)	0.033
Men	BMS	53/71	58/125	36/63	15/28	162/287 (60)	0.033
HTN	Covered	52/57	32/37	35/62	25/26	144/182 (66)	0.907
HTN	BMS	62/71	97/125	45/63	25/28	229/287 (60)	0.907
DM	Covered	21/57	9/37	15/62	13/26	58/182 (66)	0.236
DM	BMS	26/71	50/125	18/63	13/28	107/287 (60)	0.236
CHD	Covered	31/57	17/37	23/62	13/26	84/182 (66)	0.973
CHD	BMS	29/71	66/125	24/63	13/28	132/287 (60)	0.973
HLD	Covered	45/57	27/37	26/62	18/26	116/182 (66)	0.487
HLD	BMS	54/71	88/125	29/63	21/28	192/287 (60)	0.487
Smoking	Covered	46/57	33/37	37/62	20/26	136/182 (66)	0.658
Smoking	BMS	48/71	112/125	37/63	23/28	220/287 (60)	0.658
TASC II category
A	Covered	0/82	18/64	0/83	7/26	25/255 (8)	0.008
A	BMS	0/85	55/190	0/85	13/28	68/388 (15)	0.008
B	Covered	0/82	21/64	42/83	9/26	72/255 (8)	0.049
B	BMS	0/85	64/190	62/85	13/28	139/388 (15)	0.049
C	Covered	34/82	11/64	29/83	6/26	80/255 (8)	0.793
C	BMS	52/85	46/190	17/85	2/28	117/388 (15)	0.793
D	Covered	48/82	14/64	12/83	4/26	78/255 (8)	<0.001
D	BMS	33/85	25/190	6/85	0/28	64/388 (15)	<0.001

Abbreviations: BMS, bare metal stent; CHD, coronary heart disease; DM, diabetes mellitus; HLD, hyperlipidemia; HTN, hypertension; TASC, TransAtlantic Inter-Society Consensus.

Continuous data are presented as the means ± standard deviation; categorical data are given as the counts/sample (percentage).

Fisher exact test.

Femoropopliteal Disease

Overall, 135 diseased arteries in 135 patients (mean age 69 years; 95 men) were treated with covered stents and 140 diseased arteries in 140 patients (mean age 71 years; 99 men) with BMS. There was no significant difference between the groups in terms of age, sex, and comorbidities, such as hypertension (p=0.648), diabetes (p=0.902), coronary heart disease (p=0.794), hyperlipidemia (p=0.900), or smoking (p=0.770). There was no significant difference in the proportions of TASC II A (p=0.313) or C (p=0.463) lesions between the groups. The proportions of TASC II B lesions were significantly higher in the BMS group (p<0.001), while the proportions of TASC II D lesions was significantly higher in the covered stent group (p<0.001). The baseline demographics of the population with femoropopliteal disease are presented in Table 3.

Table 3.

Baseline Demographics of the Included Population With Femoropopliteal Disease.^a

	Stent Type	Authors		Overall	p^b
	Stent Type	Lammer 2013	Vartanian 2013	Overall	p^b
Age, y	Covered	68.8±8.6	68.5±10.7	—
Age, y	BMS	69.4±9.0	72±12.1	—
Men	Covered	48/72	47/63	95/135 (70)	0.950
Men	BMS	52/69	47/71	99/140 (70)	0.950
HTN	Covered	60/72	51/63	111/135 (82)	0.648
HTN	BMS	58/69	54/71	112/140 (80)	0.648
DM	Covered	25/72	26/63	51/135 (38)	0.902
DM	BMS	25/69	29/71	54/140 (39)	0.902
CHD	Covered	16/72	24/63	40/135 (30)	0.794
CHD	BMS	15/69	29/71	44/140 (31)	0.794
HLD	Covered	49/72	40/63	89/135 (66)	0.900
HLD	BMS	47/69	44/71	91/140 (65)	0.900
Smoking	Covered	50/72	57/63	107/135 (79)	0.770
Smoking	BMS	48/69	60/71	108/140 (77)	0.770
TASC II category
A	Covered	0/72	16/63	16/135 (12)	0.313
A	BMS	2/69	9/71	11/140 (8)	0.313
B	Covered	20/72	12/63	32/135 (24)	<0.001
B	BMS	29/69	34/71	63/140 (45)	<0.001
C	Covered	18/72	8/63	26/135 (19)	0.463
C	BMS	16/69	17/71	33/140 (24)	0.463
D	Covered	34/72	27/63	61/135 (45)	<0.001
D	BMS	22/69	10/71	32/140 (23)	<0.001

Abbreviations: BMS, bare metal stent; CHD, coronary heart disease; DM, diabetes mellitus; HLD, hyperlipidemia; HTN, hypertension; TASC, TransAtlantic Inter-Society Consensus.

Continuous data are presented as the means ± standard deviation; categorical data are given as the counts/sample (percentage).

Fisher exact test.

Methodological Quality and Risk of Bias

Methodological assessment of the observational studies revealed that all of them^8,9,12,13 were at low risk of bias. Both RCTs^10,11 were at low risk of bias in terms of selection, attrition, and reporting but at high risk of bias in terms of performance, detection, and bias due to being industry-sponsored. The summary and results of methodological quality assessment are demonstrated graphically in Figure 2.

Outcome Synthesis

Aortoiliac Disease

Technical success was reported in 4 studies^8,9,11,12 including 643 diseased arteries (Figure 3A). Technical success was 100% in the covered stent group and 99.7% in the BMS group (pooled RD 0.00, 95% CI −0.01 to 0.02, p=0.67). A low level of heterogeneity among the studies existed (I²=0%, p=0.93).

Primary patency was reported in 4 studies^8,9,11,12 including 643 diseased arteries (Figure 3B) and did not differ significantly (pooled OR 2.10, 95% CI 0.48 to 9.11, p=0.32). There was a high level of heterogeneity among the studies (I²=90%, p<0.001). Secondary patency was reported in 2 studies^8,9 (421 arteries, Figure 3C) and also did not differ between the groups (pooled OR 0.92, 95% CI 0.07 to 12.73, p=0.95). A high level of heterogeneity existed (I²=84%, p=0.01).

Need for reintervention was reported in 3 studies^8,11,12 including 385 diseased arteries (Figure 3D). The arteries treated with a covered stent required reintervention less commonly than those treated with a BMS (pooled OR 0.19, 95% CI 0.09 to 0.42, p<0.001). There was a low level of heterogeneity among the studies (I²=0%, p=0.45).

Major complications in the 3 studies^8,9,12 reporting these data (383 patients, Figure 3E) did not differ significantly (pooled OR 1.53, 95% CI 0.58 to 4.00, p=0.39). A low level of heterogeneity existed among the studies (I²=0%, p=0.96). Limb salvage, reported in 2 studies^8,9 (329 arteries, Figure 3F), had no significant difference between the groups (pooled OR 1.66, 95% CI 0.45 to 6.06, p=0.45). Heterogeneity was low (I²=15%, p=0.28). Two studies^8,9 (290 patients, Figure 3G) reported survival; there was no significant difference (pooled OR 1.77, 95% CI 0.94 to 3.35, p=0.08) in this outcome, and heterogeneity was low (I²=0%, p=0.95). The ABI, which was reported in 3 studies (Figure 3H),^8,11,12 was significantly higher in patients treated with covered stents (pooled MD 0.08, 95% CI 0.07 to 0.09, p<0.001). Heterogeneity was low (I²=0%, p=0.68).

Femoropopliteal Disease

Technical success in the single study¹⁰ reporting this outcome (141 diseased arteries; Figure 4A) was 100% in the covered stent group and 98.6% in the BMS group (RD 0.01, 95% CI −0.02 to 0.05, p=0.46). Primary patency, reported in 2 studies^10,13 including 275 diseased arteries (Figure 4B), was significantly higher in arteries treated with covered stents (pooled OR 1.84, 95% CI 1.11 to 3.06, p=0.02). Heterogeneity in these studies was low (I²=0%, p=0.77). Secondary patency was not reported by the included studies.

Need for reintervention was reported in 2 studies^10,13 including 275 diseased arteries (Figure 4C). The arteries treated with a covered stent required reintervention less commonly than those treated with BMS (pooled OR 0.51, 95% CI 0.30 to 0.87, p=0.01). A low level of heterogeneity existed (I²=21%, p=0.26).

Two studies^10,13 (275 patients, Figure 4D) reported the major complication rate, which did not differ between the covered stent and BMS groups (pooled OR 1.37, 95% CI 0.74 to 2.53, p=0.32). Heterogeneity was low (I²=0%, p=0.72). There was no significant difference in limb salvage between the groups (pooled OR 8.47, 95% CI 0.45 to 160.44, p=0.15) based on the 2 studies^10,13 (275 arteries, Figure 4E) reporting this outcome. One study¹⁰ (141 patients, Figure 4F) reported survival; there was no significant difference (RD 0.00, 95% CI −0.03 to 0.03, p>0.99). ABI was also reported in 1 study¹⁰ (Figure 4G), but it was significantly higher in patients treated with a covered stent (MD 0.08, 95% CI 0.00 to 0.16, p=0.04).

Sensitivity Analyses

Removing one study at a time from the analysis did not change the direction of the effect size or the overall heterogeneity for any of the outcomes except primary patency in aortoiliac disease. Removing the study of Humphries et al⁹ reduced the I² from 90% to 0% for primary patency and changed the direction of the effect size in favor of a covered stent. In fact, after excluding the study of Humphries et al,⁹ the primary patency became significantly higher in the covered stent group (pooled OR 3.68, 95% CI 2.06 to 6.59, p<0.001), with a low level of heterogeneity (I²=0%, p=0.63). The use of random or fixed effects models did not affect the direction of the effect size in any of the outcomes. Moreover, the direction of the effect size for all of the outcomes remained unchanged when ORs or RDs were calculated. The separate analyses for studies with low or moderate risk of bias did not produce a change in the direction of the effect size.

Subgroup Analyses

One RCT¹¹ enrolled 125 patients with 168 diseased aortoiliac arteries. Covered stents were associated with increased primary patency (OR 3.40, 95% CI 1.52 to 7.59, p=0.003) and higher ABI (MD 0.08, 95% CI 0.07 to 0.09, p<0.001). Moreover, reintervention was required less frequently in the covered stent group (OR 0.13, 95% CI 0.03 to 0.61, p=0.009). There was no significant difference in technical success between the groups (RD 0.00, 95% CI −0.03 to 0.03, p>0.99). The remaining outcomes were not reported.

One RCT¹⁰ enrolled 141 patients with 141 diseased femoropopliteal arteries. Covered stents were associated with increased primary patency; however, it was not statistically significant (OR 1.98, 95% CI 0.99 to 3.97, p=0.05). Covered stents were associated with higher ABI (MD 0.08, 95% CI 0.00 to 0.16, p=0.04). The reintervention rate was not significantly different between the groups (OR 0.73, 95% CI 0.32 to 1.66, p=0.45). There was no significant difference in technical success (RD 0.01, 95% CI −0.02 to 0.05, p=0.46), complications (OR 1.20, 95% CI 0.46 to 3.11, p=0.70), limb salvage (RD 0.00, 95% CI −2.94 to 2.94, p>0.99), or survival (RD 0.00, 95% CI −0.03 to 0.03, p>0.99) between the groups. Secondary patency was not reported.

Discussion

This analysis of different stent types for treatment of aortoiliac and femoropopliteal disease showed that treatment with covered stents was associated with increased primary patency in the femoropopliteal segment; however, it did not improve primary patency significantly in aortoiliac disease. Moreover, treatment with covered stents was associated with higher ABI and fewer reinterventions compared with treatment with BMS in both aortoiliac and femoropopliteal segments, whereas technical success, complications, limb salvage, and survival were similar. Overall, a low to moderate level of between-study heterogeneity was identified. Regardless of the effects models employed, the directions of the effect sizes remained consistent throughout the sensitivity and subgroup analyses for all the outcomes except primary patency in aortoiliac disease, where the direction of the effect size was changed in favor of covered stent after removing the main contributor⁹ to between-study heterogeneity. Because of this marked inconsistency of outcomes, the currently available comparative evidence is not adequately robust to reach definite conclusions.

In our study, the primary patency rates for aortoiliac disease in the covered and BMS groups were 85.9% and 80.4%, respectively. Although the pooled primary patency rate in the BMS group was similar to that reported in other studies,^16,17 in the covered stent group, the pooled primary patency was lower compared to other reported figures.^18,19 Wiesinger et al¹⁹ reported primary patency rates of 92% at 6 months and 89.8% at 12 months for a cohort of 98 patients who received PTFE-covered nitinol stents in 107 arteries. Moreover, Bosiers et al¹⁸ reported a primary patency rate of 91.1% at 1 year in a cohort of 65 patients (91 treated arteries). The lower primary patency in our analysis may be due to the longer follow-up periods in the included studies, ranging from 12 to 22 months. Furthermore, unlike the other studies, >60% of the arterial lesions in the covered stent group were TASC II C or D lesions, which may explain the lower primary patency rate in our study. Considering the small number of studies and the limited available data, no multivariate analysis was performed to assess any relationship between the TASC II lesion type and the patency related to stent type.

Technical success in both groups in our study was comparable with reports in other studies. Bosiers et al¹⁸ and Wiesinger et al¹⁹ reported technical success rates of 100% and 99%, respectively. However, it should be noted that technical success was inconsistently defined among authors. Although covered stents require larger delivery systems than BMS, which may expose the patient to a higher risk of groin complications, our findings did not show any difference in complication rates. Consistent with our findings, Grimme et al²⁰ reported no difference in complication rates between bare and covered stents.

Covered stents allow exclusion of the atheromatous plaque and endothelium, which prevents migration and proliferation of vascular smooth muscle cells and inflammatory cells through open stent struts, lessening late lumen loss.²¹ Therefore, prevention of luminal extracellular matrix deposition and intimal hyperplasia reduce the risk of restenosis.²² This theory may explain the lower reintervention rate in the covered stent group in our study.

The low level of between-study heterogeneity in our analysis can be explained by homogenous patient demographics and comorbidities among the included studies. This can potentially enhance the validity of our findings. Lack of evidence about hard clinical endpoints (such as quality of life and limb salvage) suggests that BMS may still be as good as covered stents for clinical endpoints.

Limitations

The reported outcomes of our analysis should be interpreted in the context of inherent limitations. We identified a limited number of eligible studies reporting a relatively small number of treated vessels; therefore, the available evidence is insufficient to draw solid conclusions on the comparative efficacy of covered over bare stents in lower limb PAD. Moreover, the wide confidence intervals found for the most crucial outcome measures, ie, patency and reintervention, limit our confidence on the true effect sizes. Four of the included studies were retrospective cohort studies that are inevitably subject to selection bias. The available data did not allow us to perform subgroup analysis based on anatomic parameters, such as TASC II disease classification. Long-term results of the comparative efficacy of covered stents are not currently available. Furthermore, there was a significant difference in the proportions of TASC II A, B, and D lesions between the covered stent and BMS groups. Patients treated with covered stents had more extensive disease as indicated by the TASC II classification. Different disease severity with more extensive disease in the covered stent group may be underestimating the intervention effect. It is therefore likely that the actual intervention effect is larger than the data suggest. Finally, 3 of the included studies were industry-sponsored, which can potentially put our results at risk of bias.

Conclusion

Covered stents had improved outcomes compared to BMS in the treatment of aortoiliac and femoropopliteal disease, as reflected in the need for reintervention and ABI. The primary patency was improved with covered stents in femoropopliteal disease but not in aortoiliac disease. It remains to be investigated whether such beneficial effects can be translated into improved clinical outcomes, such as limb salvage and amputation-free survival. In order to define a subgroup of patients who can benefit most from covered stents, future randomized trials should focus on outcomes based on different vascular segments and stages of TASC II classification of lower limb PAD.

Footnotes

Appendix

Search	Search Strategy^a
#1	MeSH descriptor: [stents] explode all trees
#2	(covered stent or metal stent or bare-metal stent or polytetrafluoroethylene stent or PTFE stent): TI, AB, KW
#3	#1 OR #2
#4	MeSH descriptor: [disease, peripheral arterial] explode all trees
#5	(aortoiliac or aorto-iliac or iliac or femoropopliteal or femoro-popliteal or crural): TI, AB, KW
#6	#4 OR #5
#7	#3 AND #6

This search strategy was adopted for the following databases: MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL).

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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