Umbrella review and meta‐analysis of antiplatelet therapy for peripheral artery disease

Objective: The literature on antiplatelet therapy for peripheral arterial disease has historically been summarised inconsistently, leading to conflict between international guidleines. An umbrella review and meta-analysis was performed to clearly summarise the literature, allow assessment of competing safety risks and clinical benefits, and identify weak areas for future research.

Methods: MEDLINE, EMBASE, DARE, PROSPERO and Cochrane databases were searched from inception until January 2019. All meta-analyses of antiplatelet therapy in peripheral arterial disease were included. Quality was assessed using Amstar scores, with GRADE analysis quantifying strength of evidence. Data were pooled using random-effects models.

Results: Twenty-eight meta-analyses were included. Thirty-three clinical outcomes and 41 antiplatelet comparisons in 72,181 patients were analysed. High-quality evidence showed antiplatelet monotherapy reduced non-fatal strokes and cardiovascular death in symptomatic patients (3 and 8 fewer per 1000 patients respectively, 95% CI 0–6 and 0–16), but increased risk of major bleeding (7 more per 1000, 95% CI 3–14). In asymptomatic patients, monotherapy reduced non-fatal strokes (5 fewer per 1000, 95% CI 0–8) but had no other clinical benefit. Dual antiplatelet therapy caused more major bleeding after intervention than monotherapy (37 more per 1000, 95% CI 8–102), with very low-quality evidence of improved endovascular patency (Relative Risk 4.00, 95% CI 0.91–17.68).

Conclusions: Antiplatelet monotherapy has minimal clinical benefit for asymptomatic peripheral arterial disease, and limited benefit for symptomatic disease, with clear risk of major bleeding. There is a lack of evidence to guide antiplatelet prescribing after peripheral endovascular intervention which needs addressing by adequately powered randomised trials.

Study registration: PROSPERO 2017 CRD42017084223