Sex-Based Differences in Clinical Outcomes With Edoxaban Therapy

Background Sex-based differences exist in the characteristics and prognosis of patients with atrial fibrillation (AF) and coronary artery disease (CAD). It is still unknown whether optimal antithrombotic therapy differs by sex. Objectives This study aimed to evaluate the efficacy and safety of edoxaban therapy in AF with stable CAD, according to sex category. Methods This prespecified substudy of the EPIC-CAD (Edoxaban Versus Edoxaban With Antiplatelet Agent in Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease [EPIC-CAD]) trial compared edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent). The primary outcome was net adverse clinical events (a composite of death, myocardial infarction, stroke, unplanned revascularization, or clinically relevant bleeding) at 12 months. Median follow-up was 12.0 months (IQR: 11.6-12.9). Results Of 1,040 randomized patients, 238 (22.9%) were women; in the dual-therapy group (n = 516), 110 (21.3%) were women and in the monotherapy group (n = 524), 128 (24.4%) were women. Women were older, had lower body weight, lower creatinine clearance, and more frequently met the edoxaban dose-reduction criteria. The risk of primary outcome was similar between women and men (adjusted HR [aHR]: 1.15; 95% CI: 0.71-1.87; P = 0.559). Edoxaban monotherapy significantly reduced primary events in men compared with dual therapy (aHR: 0.36; 95% CI: 0.23-0.57; P < 0.001), but not in women (aHR: 0.74; 95% CI: 0.33-1.64; P = 0.455). No significant interaction between the randomized treatment and sex was observed ( P for interaction = 0.09). Conclusions Edoxaban monotherapy reduced primary net adverse events at 12 months in men but not in women. No significant interaction with sex was observed. Further research is needed to identify sex-specific antithrombotic strategies for patients with AF and CAD.