Abstract 4369623: P2Y12 Inhibitor Monotherapy as a Safer and Equally Effective Alternative to Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention: A Comprehensive Meta-Analysis of 52,475 Patients

Background: Current guidelines recommend 12 months of DAPT after PCI in ACS patients; however, prolonged use is associated with increased bleeding risk. Emerging strategies propose shortened DAPT followed by P2Y12 inhibitor (P2Y12i) monotherapy as a safer alternative without loss of efficacy. Methods: We conducted a comprehensive systematic review of PubMed, Embase, Scopus, and Web of Science up to March 12, 2025. We included RCTs and cohort studies comparing short DAPT (≤3 months) followed by P2Y12i monotherapy versus standard DAPT (≥12 months) in ACS patients undergoing PCI. Primary outcomes were NACE, Net Clinical Benefit events, MACCE, cardiovascular death, myocardial infarction (MI), and major bleeding at 12 months. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random-effects model. Results: Thirteen studies involving 52,475 patients were included. P2Y12i monotherapy significantly reduced NACE (RR=0.77; 95% CI [0.69–0.85]; p<0.00001), Net Clinical Benefit events (RR=0.58; 95% CI [0.43–0.79]; p=0.0002), MACCE (RR=0.85; 95% CI [0.73–0.98]; p=0.03), and major bleeding (RR=0.48; 95% CI [0.36–0.64]; p<0.00001). No significant differences were observed in cardiovascular death (RR=0.81; 95% CI [0.61–1.08]; p=0.14) or MI (RR=0.97; 95% CI [0.79–1.19]; p=0.71). Conclusion: In ACS patients post-PCI, P2Y12i monotherapy after short DAPT significantly reduces adverse clinical events and bleeding, with comparable ischemic protection to standard DAPT.