Ticagrelor Monotherapy or Aspirin Plus Prasugrel After Percutaneous Coronary Intervention

Background: The 2025 American College of Cardiology/American Heart Association guidelines endorse de-escalation to ticagrelor monotherapy after percutaneous coronary intervention (PCI) for acute coronary syndromes (ACSs), whereas the 2023 European Society of Cardiology guidelines recommend 12-month dual antiplatelet therapy (DAPT) with aspirin plus prasugrel as the default strategy. Objectives: The objective of the study was to compare ischemic and bleeding outcomes between these strategies and to evaluate whether diabetes modifies their relative effects. Methods: Randomized controlled trials enrolling patients after PCI and evaluating de-escalation to ticagrelor monotherapy or 12-month DAPT (ticagrelor or prasugrel-based) were included. The primary efficacy and safety outcomes were major adverse cardiovascular or cerebrovascular events (MACCE) and major bleeding. Incidence rate ratios (IRRs) with 95% CIs were pooled using a frequentist random-effects network meta-analysis. Subgroup analyses were performed according to diabetes status. Results: Seven randomized controlled trials including 27,225 patients were included (mean age, 62 years; 23.2% women; 31.7% diabetes; 98.6% ACS). Ticagrelor monotherapy and aspirin plus prasugrel were compared indirectly through ticagrelor-based DAPT. Ticagrelor monotherapy showed similar MACCE compared with aspirin plus prasugrel (IRR: 1.09; 95% CI: 0.86-1.38), although a clinically meaningful increase in risk cannot be excluded ( P for noninferiority = 0.33); major bleeding was lower with ticagrelor monotherapy (IRR: 0.54; 95% CI: 0.37-0.80). An interaction between P2Y 12 inhibitor strategy and diabetes status was observed for MACCE ( P int = 0.04). Conclusions: In this network meta-analysis of predominantly ACS patients undergoing PCI, ticagrelor monotherapy reduced major bleeding compared with 12 months of aspirin plus prasugrel, whereas it did not meet noninferiority for MACCE. Direct randomized comparisons are warranted. (Ticagrelor Monotherapy or Aspirin Plus Prasugrel After Percutaneous Coronary Intervention: A Network Meta-Analysis; CRD420261322968 )