Antithrombotic therapy and major adverse limb events in patients with chronic lower extremity arterial disease: systematic review and meta-analysis from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy in Collaboration with the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases

INTRODUCTION The role and selection of antithrombotic therapy to improve limb outcomes in chronic lower extremity artery disease (LEAD) is still debated. We conducted a meta-analysis to examine the efficacy and safety of anti-thrombotic and more intense antithrombotic therapy on limb outcomes and limb salvage in patients with chronic LEAD. METHODS Study inclusion criteria were: enrollment of patients with LEAD, randomized allocation to more vs. less intense antithrombotic therapy [more vs. less intense single antiplatelet therapy (SAPT); dual antiplatelet therapy (DAPT) vs. SAPT; dual antithrombotic therapy vs. SAPT or oral anticoagulant]; enrolment of ≥ 200 patients; reporting of at least one of following outcomes: limb amputation or revascularization. Seven randomized studies enrolling 30'447 patients were included. RESULTS Over a median follow-up of 24 months, more vs. less intense antithrombotic therapy or placebo significantly reduced the risk of limb revascularization (relative risk [RR]: 0.89; 95% confidence interval [CI]: 0.83 - 0.94) and limb amputation (RR: 0.63, 95% confidence interval [CI]: 0.46-0.86), as well as stroke (RR: 0.82, 95% CI: 0.70-0.97). There was no statistically significant effect on the risk of myocardial infarction (RR: 0.98, 95% CI: 0.87-1.11), all-cause (RR: 0.93, 95% CI: 0.86-1.01) and cardiovascular death (RR: 0.97, 95% CI: 0.86-1.08). Risk of major bleeding increased (RR: 1.23, 95% CI: 1.04-1.44). CONCLUSION In patients with LEAD, more intense antithrombotic therapy reduces risk of limb amputation and revascularization as well as stroke, with an increase in the risk of bleeding events.