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 & 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