In patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI) while on direct oral anticoagulation (DOAC), current European and North American guidelines recommend dual therapy with a P2Y12 inhibitor but not aspirin. Results from a Swedish registry study, presented at the European Society of Cardiology (ESC) Congress 2025, shed new light on the choice of P2Y12 inhibitor in this high-risk population.

Using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and national registers, researchers analyzed 3,708 ACS patients (median age 76 years) discharged on dual therapy with a P2Y12 inhibitor plus DOAC between 2014 and 2022. Of these, 32% received ticagrelor and 68% clopidogrel.

At one year, the rates of major adverse cardiovascular events (MACE) were similar for ticagrelor and clopidogrel (adjusted HR 1.02, 95% CI 0.86–1.22). Mortality and reinfarction outcomes were also comparable.

However, bleeding occurred more often with ticagrelor (4.9% vs 3.7%; adjusted HR 1.51, 95% CI 1.03–2.20).
These findings suggest that clopidogrel may offer a safer balance of efficacy and bleeding risk compared to ticagrelor in ACS patients on DOACs undergoing PCI.