Ticagrelor versus clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention and using direct oral anticoagulants

Background For patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) using direct oral anticoagulation (DOAC), European and North American guidelines recommend dual antithrombotic treatment with a P2Y12 inhibitor but not aspirin. To our knowledge, no previous study has specifically compared ticagrelor with clopidogrel in this context. We therefore aimed to evaluate clinical outcomes using ticagrelor versus clopidogrel as part of dual anti-thrombotic treatment in ACS patients undergoing PCI. Methods In this cohort study, data were extracted from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), the Patient Register, and the Swedish Prescribed Drug Register. We included the first recorded ACS event for patients undergoing PCI with dual antithrombotic treatment during the study period (January 2014 to February 2022). The P2Y12 inhibitor at discharge defined the group. Crude and adjusted hazard ratios with 95% confidence intervals (CI) were obtained using Cox regression for outcomes within one year: major adverse cardiovascular event (MACE), all-cause mortality, myocardial reinfarction, bleeding, stroke, and stent thrombosis. Patients were censored at 14 days after discharge if they had not previously filled their P2Y12 inhibitor or DOAC prescription within six months prior to the event and also did not fill that prescription within 14 days post-discharge. Additionally, patients were censored when they filled a prescription for another P2Y12 inhibitor or for aspirin. Results In total, 3,708 patients were included (median age: 76 years; 69% male; 12% smokers; 14% diabetes; 40% ST-elevation myocardial infarction; DOAC: 70% apixaban, 19% rivaroxaban, 9% dabigatran, 2% edoxaban) (Table 1). At discharge, 1,170 (32%) patients were prescribed ticagrelor and 2,538 (68%) clopidogrel. The ticagrelor patients were younger, smoked more frequently, and had a greater incidence of ST-elevation myocardial infarction. For MACE, the ticagrelor group experienced an unadjusted 19% event rate compared to 22% for the clopidogrel group, yielding an adjusted hazard ratio of 1.02 (95% CI: 0.86–1.22) (see Table 2). Mortality rates were 6.6% with ticagrelor versus 6.2% with clopidogrel, with an adjusted hazard ratio of 1.24 (0.91–1.69). Bleeding occurred in 4.9% of patients taking ticagrelor compared to 3.7% in the clopidogrel group, with an adjusted hazard ratio of 1.51 (1.03–2.20). Myocardial reinfarction was observed in 12% of the ticagrelor group versus 15% in the clopidogrel group, with an adjusted hazard ratio of 0.97 (0.78–1.19). For stroke and stent thrombosis, the rates were 1.4% versus 1.2% and 0.3% versus 0.4%, respectively, and no significant differences were found. Conclusion In ACS patients on DOACs undergoing PCI, ticagrelor was associated with a higher bleeding risk compared to clopidogrel, with no differences in MACE, mortality, or reinfarction.