Phase 4 results on edoxaban monotherapy vs. dual therapy in AF with stable CAD

This summary is based on the presentation of Gi-Byoung Nam, MD, PhD (Seoul, Republic of Korea) at the ESC Congress 2024 - EPIC-CAD - Edoxaban monotherapy vs. dual antithrombotic therapy for atrial fibrillation and stable coronary artery disease.

Introduction and methods

Patients with AF and concomitant coronary artery disease (CAD) require anticoagulation treatment to prevent thromboembolic events and antiplatelet therapy to avoid ischemic events. To combat the risk of bleeding, current clinical guidelines recommend combined treatment with a DOAC and P2Y₁₂ inhibitor for 6–12 months after the index PCI or cardiac event. This should be followed by OAC monotherapy, but supporting evidence from RCTs on this long-term antithrombotic treatment strategy is limited.

The EPIC-CAD (Edoxaban Versus Edoxaban With antiPlatelet Agent In Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease) trial was a multicenter, open-label, adjudicator-masked, phase 4 RCT conducted in South Korea in which 1040 patients with high-risk AF (CHA₂DS₂-VASc score ≥2) and stable CAD were randomized to edoxaban monotherapy at standard dose (60 mg once daily) or dual antithrombotic therapy (DAT), consisting of edoxaban plus a single antiplatelet agent (aspirin or P2Y₁₂ inhibitor).

The primary endpoint was the frequency of net adverse clinical events (i.e., efficacy and safety outcomes), defined as a composite outcome of all-cause mortality, MI, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding (as defined by the International Society on Thrombosis and Haemostasis) at 12 months. Secondary endpoints included the individual components of the primary endpoint; a composite outcome of major ischemic events; and a composite outcome of major bleeding or clinically relevant nonmajor bleeding.

Main results

• The primary endpoint of net adverse clinical events occurred in 34 patients (Kaplan–Meier estimate: 6.8%) receiving edoxaban monotherapy (n=524) and 79 patients (Kaplan–Meier estimate: 16.2%) assigned to DAT (n=516) (HR: 0.44; 95%CI: 0.30–0.65; log-rank P<0.001).
• The estimated cumulative incidence of major ischemic events at 12 months was similar in the edoxaban monotherapy and DAT groups (1.6% vs. and 1.8%; HR: 1.23; 95%CI: 0.48–3.10).
• The estimated cumulative incidence of major bleeding or clinically relevant nonmajor bleeding at 12 months was lower in the edoxaban monotherapy group than in the DAT group (4.7% vs. 14.2%; HR: 0.34; 95%CI: 0.22–0.53).

Conclusion

In this South-Korean phase 4 trial among patients with high-risk AF and stable CAD, standard-dose edoxaban monotherapy reduced the risk of net adverse clinical events at 12 months compared with DAT. This clinical benefit was mainly driven by a lower bleeding rate, with no increase of ischemic events or deaths.

- Our reporting is based on the information provided at the ESC Congress 2024 -

The findings of this study were simultaneously published in N Engl J Med.