The efficacy and safety of dual-pathway inhibition therapy among patients with peripheral arterial disease – a meta-analysis
Abstract Background and objectives Peripheral artery disease (PAD) affects more than 200 million people worldwide and it is associated with an increased risk for cardiovascular morbidity and mortality. Current recommendations regarding the management of PAD have been controversial. Our meta-analysis investigated the efficacy of direct Xa inhibitor plus antiplatelet, also known as dual-pathway inhibition (DPI), on the individual components of major adverse cardiovascular events (stroke, myocardial infarction, and cardiovascular death) and major adverse limb events (amputation, restenosis, revascularization, and acute limb ischemia), the composite of MACE and MALE and its safety, in terms of bleeding, compared to antiplatelet therapy among patients with PAD. Methodology We performed a random-effects meta-analysis among patients with PAD comparing DPI to antiplatelet therapy. PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov were searched from their dates of inception to August 2020 for Randomized Controlled Trials. Three studies met the inclusion criteria for final analysis. The selected studies were assessed for risk of bias using the Cochrane RoB2 tool and the overall quality of evidence was assessed using the GRADE approach. Results Among patients with PAD, DPI significantly reduces the risk of adverse limb events excluding amputation (RR 0.69, 95% CI 0.57–0.83) and composite MACE and MALE (RR 0.80, 95% CI 0.69–0.93) but significantly increases risk of major bleeding (RR 1.43, 95% CI 1.06–1.93) compared to antiplatelet therapy alone. Overall, DPI did not reduce myocardial infarction, stroke, cardiovascular death, or amputation, or increase the risk of fatal bleeding. Conclusions Among patients with PAD, DPI is more effective than antiplatelet therapy alone in preventing adverse limb events excluding amputation with an increased risk of major bleeding. We recommend the use of DPI among patients with PAD who are at a low risk of bleeding. FUNDunding Acknowledgement Type of funding sources: None.