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

Abstract

Background: The literature on antiplatelet therapy for peripheral artery disease has historically been summarized inconsistently, leading to conflict between international guidelines. An umbrella review and meta-analysis was performed to summarize 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 artery disease were included. Quality was assessed using AMSTAR scores, and GRADE analysis was used to quantify the 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 that antiplatelet monotherapy reduced non-fatal strokes (3 (95 per cent c.i. 0 to 6) fewer per 1000 patients), In symptomatic patients, it reduced cardiovascular deaths (8 (0 to 16) fewer per 1000 patients), but increased the risk of major bleeding (7 (3 to 14) more events per 1000). In asymptomatic patients, monotherapy reduced non-fatal strokes (5 (0 to 8) fewer per 1000), but had no other clinical benefit. Dual antiplatelet therapy caused more major bleeding after intervention than monotherapy (37 (8 to 102) more events per 1000), with very low-quality evidence of improved endovascular patency (risk ratio 4·00, 95 per cent c.i. 0·91 to 17·68). Conclusion: Antiplatelet monotherapy has minimal clinical benefit for asymptomatic peripheral artery disease, and limited benefit for symptomatic disease, with a clear risk of major bleeding. There is a lack of evidence to guide antiplatelet prescribing after peripheral endovascular intervention.