Dual versus single antiplatelet therapy after lower extremity revascularization in peripheral artery disease: A systematic review and meta-analysis.

BACKGROUND: Peripheral artery disease (PAD) affects millions globally, with a 5.6% prevalence in 2015 impacting 236 million adults, rising above 10% in those over 60 due to factors like diabetes and smoking. Post-revascularization, single antiplatelet therapy (SAPT) is standard, but dual antiplatelet therapy (DAPT) may improve outcomes, though duration and bleeding risks are unclear. The 2024 American College of Cardiology/American Heart Association guidelines endorse short-term DAPT, yet evidence gaps remain in comparative efficacy and safety. We hypothesized that DAPT reduces cardiovascular events and reinterventions vs SAPT without significantly elevating bleeding in PAD patients' post-lower extremity revascularization. AIM: To evaluate the efficacy and safety of DAPT vs SAPT in PAD patients' post-revascularization. METHODS: This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, searching PubMed, EMBASE, and ScienceDirect up to July 2025. Included were randomized controlled trials (RCTs) and cohort studies from various global settings (e.g., hospitals, tertiary care) comparing DAPT (aspirin plus P2Y12 inhibitor for > 1 month) to SAPT in symptomatic PAD patients undergoing endovascular or surgical revascularization (n up to 28244 participants selected via eligibility criteria). Data were pooled using random-effects models for risk ratio (RR) with 95%CI; heterogeneity was assessed via the I² statistic. Quality appraisal used Risk of Bias in Non-randomized Studies of Interventions for cohorts and Risk of Bias 2.0 for RCTs; certainty was evaluated via Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Twelve studies (3 RCTs, 9 cohorts, conducted 2010-2025 with follow-ups of 6 months to 5 years) were included. DAPT showed no significant difference but a trend toward reduced all-cause mortality (RR: 0.52, 95%CI: 0.27-1.01, P = 0.05, DAPT of 298/9545 events vs SAPT of 165/566 events) or stroke (RR: 0.72, 95%CI: 0.30-1.72, P = 0.46, DAPT of 16/3729 events vs SAPT of 41/7673 events) vs SAPT. DAPT significantly reduced cardiac mortality (RR: 0.46, 95%CI: 0.27-0.80, P = 0.006, DAPT of 78/2903 events vs SAPT of 171/1465 events, risk difference: -5.4%), myocardial infarction (RR: 0.82, 95%CI: 0.71-0.94, P = 0.004, DAPT of 233/7704 events vs SAPT of 262/9130 events, risk difference: -1.8%), and major reintervention (RR: 0.58, 95%CI: 0.35-0.98, P = 0.04, DAPT of 803/205 events vs SAPT of 1197/4 events, risk difference: -42%). Bleeding showed no difference (RR: 1.12, 95%CI: 0.42-3.03, P = 0.82, DAPT of 195/2775 events vs SAPT of 202/8234 events). Heterogeneity was high (I 2 = 59%-97%). Quality revealed moderate to serious bias in cohorts and some concerns in RCTs; GRADE certainty moderate for cardiac mortality, myocardial infarction, reintervention, low for others due to inconsistency and imprecision. CONCLUSION: DAPT reduces cardiac mortality, myocardial infarction, and major reintervention risks compared to SAPT in PAD post-revascularization without apparent bleeding increase, though limited by heterogeneity and low certainty for some outcomes.