P2Y12 Inhibitor or Aspirin Following Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Purpose Current guidelines recommend aspirin monotherapy for secondary prevention following dual antiplatelet therapy (DAPT) completion after percutaneous coronary intervention (PCI). However, recent evidence suggests P2Y12 inhibitor monotherapy may offer superior cardiovascular protection. Methods We conducted a literature search for randomized controlled trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy after DAPT discontinuation in post-PCI patients. Electronic databases were searched up to September 2025. Primary outcomes included major adverse cardiac and cerebrovascular events (MACCE) and net adverse clinical events (NACE). The summary effect measures were estimated using a random-effects model. Results Four trials encompassing 22,022 patients were included. P2Y12 inhibitor monotherapy significantly reduced MACCE compared to aspirin monotherapy (RR 0.73, 95% CI 0.64–0.83) and NACE (RR 0.82, 95% CI 0.74–0.91). Secondary analysis demonstrated significant reductions in myocardial infarction (RR 0.59, 95% CI 0.47–0.75), any stroke (RR 0.66, 95% CI 0.49–0.88), ischemic stroke (RR 0.69, 95% CI 0.49–0.97), stent thrombosis (RR 0.60, 95% CI 0.37–0.99), and target vessel revascularization (RR 0.76, 95% CI 0.59–0.99). No significant differences were observed in mortality or major bleeding outcomes. Conclusions P2Y12 inhibitor monotherapy provides superior cardiovascular protection compared to aspirin monotherapy following DAPT completion in post-PCI patients, with comparable safety profiles. These findings challenge traditional aspirin-centered secondary prevention strategies and support broader clinical adoption of P2Y12 inhibitor monotherapy.