Ticagrelor or clopidogrel in atrial fibrillation patients undergoing percutaneous coronary intervention for myocardial infarction

Abstract Background Contemporary guidelines recommend clopidogrel as the P2Y12 receptor inhibitor of choice in atrial fibrillation (AF) patients with acute coronary syndrome and/or percutaneous coronary intervention (PCI) who require concomitant oral anticoagulation (OAC). Conversely, the use of ticagrelor or prasugrel in these settings is discouraged. Purpose To examine the efficacy and safety of more potent P2Y12 inhibitors (ticagrelor or prasugrel) versus clopidogrel in patients with AF on OAC undergoing PCI for myocardial infarction. Methods We conducted a Danish, nationwide, registry-based cohort study of patients on an OAC for presumed AF who underwent PCI for myocardial infarction from 2011 through 2019. Only individuals discharged on a P2Y12 inhibitor and an OAC were included, while those receiving a P2Y12 inhibitor prior to hospitalization were excluded. The primary efficacy outcome was major adverse cardiovascular events, defined as a composite of death from any cause, recurrent myocardial infarction, repeat revascularization, or stroke, while the primary safety outcome was bleeding requiring hospitalization. Death from any cause was the main secondary outcome. Absolute and relative risks for outcomes at 1 year were calculated through multivariable logistic regression with average treatment effect modeling. Efficacy outcomes were standardized for the CHA2DS2-VASc score and aspirin use while bleeding outcomes were standardized for the HAS-BLED score and proton-pump inhibitor use. Results A total of 2259 patients were included of whom 1918 (84.9%) were discharged on clopidogrel and 341 (15.1%) on ticagrelor or prasugrel (the latter two were merged into one group because only 38 persons were discharged on prasugrel). Individuals who received the more potent P2Y12 inhibitors were younger (median age 70 vs. 74 years), more often men (76.0% vs. 70.8%), and less often had prior coronary artery disease (5.6% vs. 9.6%) than those who received clopidogrel. The standardized risk of major adverse cardiovascular events was significantly lower in patients discharged on ticagrelor or prasugrel compared with clopidogrel (standardized absolute risk, 15.8% vs. 19.6%; relative risk, 0.81, 95% confidence interval [CI], 0.68 to 0.93; P=0.003), while the risk of bleeding did not differ (standardized absolute risk, 5.2% vs. 5.2%; relative risk, 1.00, 95% confidence interval, 0.69 to 1.32; P=0.99) (Figure). The risk of death was significantly lower in the group of patients who were prescribed ticagrelor or prasugrel compared with clopidogrel (P<0.001). Conclusions In patients with AF on OAC who had undergone PCI for myocardial infarction, discharge on ticagrelor or prasugrel versus clopidogrel was associated with reduced ischemic risk, but not an increased bleeding risk. While these findings appear to support an individualized choice of P2Y12 inhibitor in this population, they should be interpreted with caution given the observational nature of the study.Figure