Aspirin or P2Y12 Inhibitor Monotherapy After Percutaneous Coronary Intervention for Acute Coronary Syndromes

In patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), shortening dual antiplatelet therapy (DAPT) duration reduces bleeding, but the relative benefit of maintaining aspirin or P2Y12 inhibitor monotherapy is debated. The authors sought to compare the net benefits of aspirin vs P2Y12 inhibitor monotherapy after short DAPT. Randomized trials of short DAPT in ACS patients undergoing PCI were identified. The primary outcome was trial-defined net adverse clinical events (NACE), a composite of ischemic and bleeding events. Secondary outcomes included single components of the primary endpoint. Pairwise and network meta-analyses were conducted. Heterogeneity sources were explored through sensitivity analyses. Twenty-three studies (N = 45,394) were included. Median DAPT duration was 4.8 (3.0-6.0) months and 2.2 (1.0-3.0) months in trials of aspirin and P2Y12 inhibitor monotherapy, respectively. Significant interaction between the 2 monotherapies was detected for NACE (Pint = 0.026) and any bleeding (Pint = 0.008), as being reduced by P2Y12 inhibitor (incidence rate ratio IRR: 0.78; 95% CI: 0.64-0.95 for NACE; IRR: 0.56; 95% CI: 0.46-0.67 for any bleeding), but not aspirin monotherapy. At indirect comparison, P2Y12 inhibitor monotherapy reduced NACE (IRR: 0.77; 95% CI: 0.62-0.95) and any bleeding (IRR: 0.68; 95% CI: 0.48-0.95) compared with aspirin monotherapy. Differences for bleeding endpoints, but not NACE, were mitigated when accounting for DAPT duration. In patients with ACS undergoing PCI, the benefits of short DAPT varied according to the subsequent monotherapy administered, with P2Y12 inhibitor monotherapy significantly reducing NACE, any bleeding, and major bleeding, whereas aspirin monotherapy had neutral results. (Dual Antiplatelet Therapy De-Escalation Followed By Aspirin or P2Y12 Inhibitor Monotherapy after Percutaneous Coronary Intervention for Acute Coronary Syndrome: a Systematic Review and Meta-analysis; CRD42025645844).