Net Clinical Benefit of Edoxaban Versus Apixaban in Patients With Atrial Fibrillation and Coronary Artery Disease

Non-vitamin K antagonist oral anticoagulants (NOACs) have become the standard of care for the prevention of thromboembolic events in patients with AF. In patients with AF and concomitant CAD, the choice of oral anticoagulant is particularly important because clinicians must balance the risks of thromboembolism, coronary ischemic events, as well as bleeding. Among available NOACs, apixaban and edoxaban share a common mechanism of factor Xa inhibition but differ substantially in dosing regimen, pharmacokinetic profile, and degree of renal elimination. In the recent COBRRA trial, apixaban was associated with significantly lower clinically relevant bleeding compared with rivaroxaban in patients with acute venous thromboembolism, without compromising efficacy against recurrent thromboembolism. Although these data support apixaban as an important benchmark NOAC, direct randomized comparisons between edoxaban and apixaban are lacking, particularly in patients with AF and coexisting CAD. Once-daily dosing and lower renal elimination fraction of edoxaban may offer practical advantages, particularly in elderly patients or those with impaired renal function, by potentially improving adherence and simplifying dose adjustment. Whether these pharmacological differences translate into meaningful differences in overall clinical outcomes remains uncertain. Given that anticoagulation strategies inherently require balancing thromboembolic protection against bleeding risk, evaluation using a net clinical outcome is clinically most relevant. Therefore, this randomized controlled trial is designed to determine whether edoxaban-based therapy is non-inferior to apixaban with respect to NACE, a composite of death, thromboembolic, and major bleeding outcomes in patients with AF and concomitant CAD.