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

Abstract Aims 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 antithrombotic and more intense antithrombotic therapy on limb outcomes and limb salvage in patients with chronic LEAD. Methods and results Study inclusion criteria were: enrolment of patients with LEAD, randomized allocation to more vs. less intense antithrombotic therapy [more vs. less intense single-antiplatelet therapy (SAPT); dual-antiplatelet therapy 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. 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% 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 the risk of limb amputation and revascularization as well as stroke with an increase in the risk of bleeding events.