Outcomes of Clopidogrel vs Potent P2Y12 Inhibitors in Patients With ACS and AF on OAC

Introduction: Atrial fibrillation (AF) and acute coronary syndromes (ACS) frequently coexist, presenting a significant clinical challenge due to the need for both anticoagulation and antiplatelet therapy. The combination of oral anticoagulants (OAC) with DAPT leads to a heightened risk of bleeding, prompting recent guidelines to recommend using an OAC plus a P2Y12 inhibitor, preferably clopidogrel, to minimize this risk. However, limited data exist on the safety and efficacy of potent P2Y12 inhibitors, such as ticagrelor and prasugrel, when combined with OAC in this population. This study aims to evaluate and compare the outcomes of clopidogrel versus potent P2Y12 inhibitors in patients with ACS and AF who are on concomitant OAC.


Methods: This retrospective cohort study includes adult patients with confirmed ACS and AF who received either clopidogrel or a potent P2Y12 inhibitor in combination with an OAC upon discharge. The primary endpoint is the incidence of bleeding events leading to readmission or unplanned discontinuation of therapy of OAC, P2Y12 inhibitor, or both. Secondary endpoints include the recurrence of major adverse cardiovascular events (MI or stroke, or all-cause mortality) and stent thrombosis as a separate secondary endpoint.


Results: The analysis of collected data showed no statistically significant differences between the clopidogrel and potent P2Y12 groups for primary or secondary endpoints. Our findings suggest that, when combined with OAC, more potent P2Y12 inhibitors may not provide additional benefit over clopidogrel in terms of reducing ischemic events or improving safety outcomes.


Conclusions: This study contributes to the small but growing body of literature evaluating combinations of OAC with clopidogrel versus potent P2Y12 inhibitors. It offers some insight into real-world clinical outcomes. Although no statistically significant safety or efficacy differences were observed, the numerically lower rate of MACE in the potent P2Y12 group may reflect enhanced antiplatelet efficacy, warranting further investigation.