Drug-eluting balloon angioplasty versus uncoated balloon angioplasty for peripheral arterial disease of the lower limbs.

backgroundAtherosclerotic peripheral arterial disease (PAD) can lead to chronic limb-threatening ischemia (CLTI) and limb loss. Treatments include lifestyle modifications, medications, and both open and minimally invasive operative approaches, including balloon angioplasty. Drug-eluting balloon (DEB) angioplasty is a promising alternative to uncoated balloon angioplasty for treating PAD. Ballooning and coating the inside of atherosclerotic vessels with cytotoxic agents inhibits cellular mechanisms responsible for atherosclerosis and neointimal hyperplasia, thereby preventing or postponing its complications. Although economic analyses may have demonstrated the cost-effectiveness of DEB angioplasty, they remain considerably more expensive than uncoated balloons, and there is uncertainty around their effectiveness. This is an update of our previously published 2016 review.

objectivesTo evaluate the benefits and harms of DEB angioplasty compared with uncoated, plain old balloon angioplasty (POBA) in people with symptomatic lower-limb PAD. SEARCH

methodsWe systematically searched the following databases for randomized controlled trials and controlled clinical trials: Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Ovid, and CINAHL EBSCO. We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov. We used the bibliographies of relevant papers to identify other studies. The most recent searches were carried out on 13 March 2023. SELECTION CRITERIA: We included randomized controlled trials comparing DEB angioplasty with POBA for intermittent claudication or critical limb ischemia (CLI). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome was amputation. Our secondary outcomes included amputation-free survival, secondary vessel patency, change in ankle-brachial index (ABI), change in quality of life (QoL), change in functional walking ability, and all-cause mortality. We used GRADE to assess the certainty of evidence for selected outcomes (amputation, secondary vessel patency including target lesion revascularization and binary restenosis, change in ABI, and all-cause mortality). MAIN

resultsA total of 31 trials randomizing 5292 participants met the inclusion criteria. Nineteen trials included femoropopliteal arterial lesions, nine included tibial arterial lesions, and three included both. The trials were carried out in Europe, the US, China, Singapore, Jordan, Japan, and New Zealand. All trials used paclitaxel. All but four trials were industry-sponsored. There was heterogeneity in the frequency of stent deployment and antiplatelet regimens between trials. Participants were followed up for up to five years. There were better outcomes with DEB angioplasty for target lesion revascularization at one year, from 204 per 1000 lesions with POBA to 80 per 1000 lesions with DEB angioplasty (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.28 to 0.41; 23 studies, 4172 participants; P < 0.00001; low-certainty evidence). DEB angioplasty was also superior for binary restenosis at one year, from 443 per 1000 vessels with POBA to 187 per 1000 vessels with DEB angioplasty (OR 0.29, 95% CI 0.23 to 0.38; 8 studies, 1288 participants; P < 0.00001; moderate-certainty evidence). There was no difference between DEB angioplasty and POBA in amputation at one year, from 16 per 1000 participants with POBA to 22 per 1000 participants with DEB angioplasty (OR 1.45, 95% CI 0.91 to 2.29; 27 studies, 4469 participants; P = 0.12; moderate-certainty evidence); all-cause mortality, from 45 per 1000 participants with POBA to 44 per 1000 participants with DEB angioplasty (OR 0.97, 95% CI 0.71 to 1.32; 25 studies, 4312 participants; P = 0.83; moderate-certainty evidence); or change in ABI, from 0.1 to 0.35 higher with POBA and 0.03 higher to 0.03 lower with DEB angioplasty (mean difference (MD) 0, 95% CI -0.03 to 0.03; 5 studies, 1156 participants; P = 0.96; moderate-certainty evidence), although none of the studies were powered to detect a significant difference in these clinical endpoints. AUTHORS'

conclusionsMeta-analysis of 31 trials with 5292 participants demonstrated that there may be evidence of an advantage of DEB angioplasty compared with POBA in several anatomic endpoints including late lumen loss, target lesion revascularization (low-certainty evidence), and binary restenosis (moderate-certainty evidence). Conversely, there may be little to no evidence of advantage with DEB angioplasty for clinical endpoints such as amputation (moderate-quality evidence), amputation-free survival, death (moderate-quality evidence), change in ABI (moderate-quality evidence), QoL, or functional walking ability. Well-designed randomized trials with long-term follow-up are needed to further compare DEB angioplasty with POBA adequately for both anatomic and clinical study endpoints.