A recent study has found that edoxaban monotherapy is more effective than dual therapy with a single antiplatelet agent for patients with high-risk atrial fibrillation (AF) and stable coronary artery disease (CAD).
The findings were presented during a Hot Line session at the ESC Congress 2024 and published simultaneously in the New England Journal of Medicine.
Study Overview
The EPIC-CAD trial, an investigator-initiated, open-label, randomized trial, aimed to compare the effectiveness of edoxaban monotherapy to the combination of edoxaban and a single antiplatelet agent. Eligible participants included patients with high-risk AF, defined by a CHA2DS2-VASc score of 2 or higher, and stable CAD. For those with a history of revascularization, they had to be at least 12 months post-acute coronary syndrome or six months post-chronic angina.
Patients were randomly assigned in a 1:1 ratio to receive either standard-dose edoxaban (60 mg once daily or 30 mg once daily with dose-reduction criteria) or dual therapy with standard-dose edoxaban plus either aspirin or clopidogrel.
Primary And Secondary Endpoints
The primary endpoint of the study was the net composite outcome of death from any cause, stroke, systemic embolism, myocardial infarction, unplanned revascularization, and major or clinically relevant non-major bleeding within one year after randomization. Key secondary endpoints included the individual components of the primary endpoint, a composite of major ischemic events, and a composite of major and clinically relevant non-major bleeding.
Study Population
A total of 1,040 patients were randomized from 18 major cardiac centers in South Korea. The average age of participants was 72 years, with 23% being women. The mean CHA2DS2-VASc score was 4.3, and the mean HAS-BLED score was 2.1, indicating a moderate risk of bleeding. Two-thirds of the participants had previously undergone revascularization, with a median time since the last procedure of 53 months. Among those in the dual therapy group, 62% received aspirin while 38% received clopidogrel.
Key Findings
Over the 12 months following randomization, edoxaban monotherapy significantly reduced the risk of the primary endpoint by 56% compared to dual therapy (6.8% vs. 16.2%; hazard ratio [HR] 0.44; 95% confidence interval [CI] 0.30−0.65; p<0.001).
This reduction was primarily due to a 66% decrease in the risk of major bleeding or clinically relevant non-major bleeding with edoxaban monotherapy compared to dual therapy (4.7% vs. 14.2%; HR 0.34; 95% CI 0.22−0.53). The rates of major ischemic events were similar between the two groups, with 1.6% in the edoxaban monotherapy group and 1.8% in the dual therapy group (HR 1.23; 95% CI 0.48−3.10). Additionally, there was no significant difference in all-cause mortality between the two groups (0.6% for monotherapy vs. 0.7% for dual therapy; HR 1.29; 95% CI 0.29−5.76).
Implications of The Study
Dr. Gi-Byoung Nam, a presenter of the study, noted that the findings align with the AFIRE trial, which indicated that rivaroxaban monotherapy was non-inferior to dual therapy for efficacy and superior for safety in patients with AF and stable CAD. He emphasized that the EPIC-CAD trial provides new evidence regarding the appropriate antithrombotic strategy using standard-dose edoxaban for treating patients with AF and stable CAD.
Conclusion
The EPIC-CAD trial highlights the potential benefits of edoxaban monotherapy over dual antithrombotic therapy in reducing adverse clinical events for patients with high-risk atrial fibrillation and stable coronary artery disease. As the study adds to the growing body of evidence regarding anticoagulation strategies, it underscores the need for continued research to optimize treatment for this patient population.