Potent P2Y12 Inhibitor Monotherapy Versus Dual Antiplatelet Therapy After Percutaneous Coronary Intervention for Acute Coronary Syndromes: A Systematic Review and Meta-Analysis

Background The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) remains debated. While DAPT with aspirin and a P2Y12 inhibitor prevents ischemic events, it increases bleeding risk. This meta-analysis evaluates whether early aspirin discontinuation with P2Y12 inhibitor monotherapy offers comparable efficacy and improved safety versus standard long-term DAPT. Methods This review, conducted according to PRISMA guidelines, searched PubMed, Cochrane Central and Clinicaltrials.gov up to September 2025 for RCTs comparing short-term DAPT (≤3 months) followed by P2Y12 inhibitor monotherapy with standard-duration DAPT (≥6-12 months). Outcomes included NACE, MACE, all-cause and cardiovascular mortality, myocardial infarction, stroke, stent thrombosis, and BARC 3 or 5 bleeding. Random-effects models were applied to estimate pooled risk ratios and 95% CIs. Results Ten RCTs involving 35,277 patients were included. Compared with standard DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy significantly reduced NACE (RR = 0.80, 95% CI 0.71-0.90; p = 0.0002; I 2 = 38%), and BARC type 3 or 5 bleeding (RR = 0.48, 95% CI 0.40-0.58; p < 0.001; I 2 = 0%), without significant differences in MACE (RR: 1.01 0.86, 1.19; p = 0.87; I 2 = 41%) or all-cause mortality (RR: 0.96 0.80, 1.16; p = 0.69; I 2 = 4%). Conclusion Early transition to P2Y12 inhibitor monotherapy after 1–3 months of DAPT in ACS patients undergoing PCI significantly reduces bleeding without increasing ischemic events. Ticagrelor- or prasugrel-based monotherapy represents a safe and effective alternative to conventional 12-month DAPT.