Optimal timing of aspirin discontinuation after acute coronary syndrome treated with percutaneous coronary intervention: a systematic review and meta-analysis

Background In patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), abbreviated dual antiplatelet therapy (DAPT) reduces bleeding as compared with standard DAPT. Still, the optimal timing of aspirin discontinuation remains uncertain. We aimed to compare the net benefits of aspirin discontinuation timing in short DAPT followed by P2Y 12 inhibitor monotherapy versus standard DAPT. Methods We performed pairwise and network meta-analyses (NMAs) to directly and indirectly compare short DAPT (aspirin-free, <1 month, 1-month and 3-month DAPT) followed by P2Y 12 inhibitor monotherapy with 12-month DAPT. The primary endpoint was study-defined net adverse clinical events (NACE), a composite of ischaemic and bleeding outcomes. Secondary outcomes included major bleeding and study-defined major adverse cardiovascular events (MACE). The probability of being the best strategy was ranked according to the surface under the cumulative ranking curve. Results 11 trials (n=34 283) were included. Short DAPT followed by P2Y 12 inhibitor monotherapy reduced NACE compared with standard DAPT (risk ratio (RR) 0.77; 95% CI 0.66 to 0.89), mainly driven by major bleeding (RR 0.46; 95% CI 0.36 to 0.58). In NMA, all individual short DAPT strategies followed by P2Y 12 inhibitor monotherapy, except aspirin-free, reduced NACE, with no significant differences between them. Yet, aspirin discontinuation within<1 month ranked highest for the primary endpoint. No significant difference in MACE was observed among DAPT strategies; however, 3-month DAPT consistently ranked highest for MACE and for individual ischaemic endpoints. Conclusions In patients with ACS undergoing PCI, short DAPT followed by P2Y 12 inhibitor monotherapy is superior to standard DAPT with respect to NACE. Although a brief period of DAPT appears warranted after ACS, the optimal timing of aspirin discontinuation remains uncertain. While earlier aspirin discontinuation may be associated with greater net clinical benefit owing to reduced bleeding, 3-month DAPT may be associated with more favourable ischaemic outcomes, underscoring the importance of individualising DAPT duration according to bleeding and ischaemic risk. PROSPERO registration number CRD420251180854.