Total Clinical Event Burden with Edoxaban Monotherapy versus Dual Antithrombotic Therapy in Atrial Fibrillation and Stable Coronary Artery Disease: Insights from the EPIC‐CAD Trial

Background Oral anticoagulation (OAC) is essential for stroke prevention in atrial fibrillation (AF), whereas antiplatelet therapy remains standard for coronary artery disease (CAD), raising concerns about bleeding when both are combined. The effect of these regimens on recurrent events, reflecting cumulative disease burden, has not been fully evaluated. Methods This post‐hoc analysis of the EPIC‐CAD (Edoxaban vs. Edoxaban with antiPlatelet agent In patients with atrial fibrillation and Chronic stable Coronary Artery Disease) trial included 1,040 patients with AF and stable CAD randomized to edoxaban monotherapy or edoxaban plus a single antiplatelet agent. The primary endpoint was the total number of net adverse clinical events at 12 months. Results Over a median follow‐up of 12.1 months, 155 total events occurred (123 first, 32 subsequent). Event rates were lower with edoxaban monotherapy than with dual therapy (9.4 vs. 19.8 per 100 person‐years; incidence rate ratio [IRR], 0.47; 95% CI, 0.34–0.67). Monotherapy reduced first events (IRR, 0.46; 95% CI, 0.32–0.68) and showed a lower cumulative hazard of total events (hazard ratio, 0.48; 95% CI, 0.32–0.71; P <0.001). Bleeding was the predominant event type in both groups but occurred more often with dual therapy (85.7% vs. 55.3%; P <0.001). Rates of ischemic events and mortality were similar between groups. Conclusions Edoxaban monotherapy significantly reduced the overall burden of clinical events compared with dual antithrombotic therapy in patients with AF and stable CAD. Bleeding complications were more frequent than ischemic events, emphasizing the need to minimize bleeding risk in this population.