P2Y12 inhibitor monotherapy after abbreviated dual antiplatelet therapy following percutaneous coronary intervention: a meta-analysis

BACKGROUND AND AIMS: After percutaneous coronary intervention (PCI), growing evidence supports P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) as a safer and equally effective antiplatelet strategy compared with continued DAPT. However, the optimal timing of aspirin discontinuation remains uncertain. METHODS: A systematic review and meta-analysis of randomized controlled trials investigating different timings of aspirin discontinuation after a short course of DAPT in PCI patients, compared with continued DAPT, was conducted. Pairwise random-effects and network meta-analyses were performed. The primary endpoint was major adverse cardiovascular events (MACE). Secondary endpoints included major bleeding, major or minor bleeding, net adverse cardiovascular events (NACE), all-cause death and myocardial infarction. The study was registered in PROSPERO (CRD420251140207). RESULTS: Eleven randomized trials including 37,443 patients were identified. In pairwise analyses, compared with 12-month DAPT, there were no significant differences in the risk of MACE with aspirin discontinuation at either ≤1 month (risk ratio RR 1.01; 95% confidence interval CI 0.85-1.20) or 3 months (RR 0.95; 95% CI 0.67-1.36), with no significant differences between discontinuation timings. Both major and major or minor bleeding were significantly reduced with ≤1-month (RR 0.46; 95% CI 0.23-0.94; P = 0.038 and RR 0.43; 95% CI 0.36-0.51; P < 0.001, respectively) and 3-month (RR 0.59; 95% CI 0.39-0.89; P = 0.027 and RR 0.57; 95% CI 0.53-0.60; P = 0.005, respectively) discontinuation, with a more pronounced reduction in major or minor bleeding with ≤1-month discontinuation (P = 0.044 for interaction). NACE was significantly reduced with ≤1-month discontinuation, and no significant differences between discontinuation timings emerged. Network meta-analyses yielded consistent results, and for major or minor bleeding, the indirect comparison showed superiority of ≤1-month over 3-month aspirin discontinuation (RR, 0.75; 95% CI, 0.57-0.99; P = 0.044). In a sensitivity analysis restricted to acute coronary syndromes, early aspirin discontinuation was associated with a higher risk of stent thrombosis (RR 1.81; 95% CI 1.15-2.84; P = 0.019), with the excess risk observed mainly with very early aspirin discontinuation (<1 month). CONCLUSIONS: Aspirin discontinuation at either ≤1 or 3 months with continued P2Y12 inhibitor monotherapy is associated with similar MACE, lower bleeding, and lower NACE compared with continued DAPT. Discontinuation within the first month may confer additional bleeding benefit, but at the cost of excess stent thrombosis, particularly in patients at higher ischaemic risk.