Meta-Analysis Comparing Potent Oral P2Y12 Inhibitors versus Clopidogrel in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

Background: In patients with atrial fibrillation (AF) receiving percutaneous coronary intervention (PCI), current guidelines recommend against combining potent oral P2Y12 inhibitors (i.e. ticagrelor or prasugrel) with oral anticoagulant (OAC) therapy, but the evidence is limited. Objective: The aim of this meta-analysis was to compare the efficacy and safety of potent oral P2Y12 inhibitors with clopidogrel in patients receiving OAC therapy for AF after a recent PCI. Methods: Electronic databases were searched for randomized controlled trials (RCT) reporting outcomes according to the P2Y12 inhibitor used. Major or clinically relevant non-major bleeding were the safety endpoints, while the efficacy outcomes were major adverse cardiovascular events (MACE). The potent oral P2Y12 inhibitors prasugrel and ticagrelor were compared with clopidogrel. A subgroup analysis was conducted to evaluate the differences between patients treated with dual antithrombotic therapy (DAT) versus triple antithrombotic therapy (TAT). Results: Four RCTs that included 10,057 patients were included in this analysis. Potent oral P2Y12 inhibitors were associated with a significant increase in major or clinically relevant non-major bleeding compared with clopidogrel (risk ratio [RR] 1.30, 95% confidence interval [CI] 1.06–1.59, p = 0.01; number needed to harm 18, 95% CI 12–36). This finding was consistent regardless of the concomitant antithrombotic therapy (DAT vs. TAT; p = 0.69). The risk of MACE did not differ between potent oral P2Y12 inhibitors and clopidogrel (RR 1.02, 95% CI 0.57–1.82). Conclusions: In patients receiving OAC therapy for AF after a recent PCI, potent oral P2Y12 inhibitors increase the risk of clinically relevant bleeding compared with clopidogrel, with no evident benefit in terms of MACE reduction.