BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is standard of care after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS). Although aspirin discontinuation after at least 1 month of DAPT reduces bleeding without increasing ischemic events, the safety of aspirin withdrawal before the first 30 days after PCI remains uncertain. METHODS: Online databases were searched through December 2025 to identify randomized controlled trials (RCTs) comparing aspirin-free P2Y12 inhibitor monotherapy (MAPT) initiated within 30 days after PCI versus standard DAPT in ACS patients. Outcomes were assessed during short-term (0-30 days) and longer-term follow-up (31 days to 12 months). Random-effects models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Three RCTs comprising 10,736 patients were included. Within 30 days after PCI, aspirin discontinuation was associated with a higher risk of myocardial infarction (OR: 2.12; 95% CI: 1.31-3.44), without a reduction in bleeding compared with DAPT. No significant differences were observed in other ischemic, composite or mortality outcomes. During longer-term follow-up, MAPT was associated with significant reductions in bleeding outcomes and net adverse clinical events, without an increase in ischemic outcomes. CONCLUSIONS: In ACS patients undergoing PCI with DES, aspirin discontinuation within 30 days did not reduce bleeding and was associated with a higher risk of myocardial infarction. These findings suggest the first 30 days after PCI may represent a period of heightened ischemic vulnerability and routine aspirin withdrawal during this early phase should be interpreted with caution.
Murtafa et al. (Wed,) studied this question.