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.The AMSTAR (A MeaSurement Tool to Assess systematic Reviews) measurement tool 17,18 was used to assess the quality of included meta-analyses. AMSTAR is a validated

Single versus dual antiplatelet therapy following peripheral arterial endovascular intervention for chronic limb threatening ischaemia: Retrospective cohort study

“…Major bleeding events showed no difference between the groups. The overall rate of major bleeding was 54 per 1000 patients which is similar to that reported in previous randomised trials [1]. The sample size in this study is therefore too small to detect a significant difference, but it is reassuring that there is no large discrepancy.…”

“…Antiplatelet therapy following peripheral arterial endovascular intervention lacks high-quality evidence to guide practice [1]. This is surprising given the large number of randomised trials to guide antiplatelet practice in other areas of treatment for peripheral arterial disease, and causes conflict between recommendations in guidelines [2,3].…”

“…This group is vastly under-represented in previous case series. Moreover, long (over 6 months) durations of antiplatelet therapy was used in these studies, however clinical practice varies worldwide and many UK units, including ours, used short (less than 6 months) courses [1,11].…”

Anticoagulation in Peripheral Artery Disease: Are We There Yet?

“…Among trials and studies that tested oral anticoagulants in PAD, the Warfarin and Antiplatelet Vascular Evaluation (WAVE) and the Dutch By-pass Oral anticoagulants or Aspirin study (Dutch BOA) are the landmark trials, as they are the largest and best designed studies. [10][11][12] The WAVE trial enrolled both claudicant and critically ischaemic patients, randomisation was warfarin or acenocoumarol plus antiplatelet therapy versus antiplatelet alone. In a cohort of 2,161 Although it did not reach statistical significance, the rate of amputations appeared to be lower in patients receiving VKAs after a venous bypass (6.6% versus 9.3%; HR 0.72; 95% CI [0.5-1.01]), and the composite outcome of vascular death, MI, stroke or amputation (HR 0.89; 95% CI [0.75-1.06]) was also reduced.…”

“…13 A meta-analysis including eight trials comparing antiplatelet versus anticoagulation, confirmed that the addition of an anticoagulant to an antiplatelet drug leads to an increased patency rate of vein bypass at the cost of a higher incidence of bleeding complications. 10 Contrary patients undergoing prosthetic bypass grafts benefitted more from antiplatelet monotherapy than anticoagulation.…”