Edoxaban monotherapy reduced net adverse clinical events compared with edoxaban plus a single antiplatelet agent, when used as long-term antithrombotic therapy, in patients with high-risk atrial fibrillation (AF) and stable coronary artery disease (CAD), according to late-breaking research presented in a Hot Line session today at ESC Congress 2024. The EPIC-CAD trial is simultaneously published in the New England Journal of Medicine.
There was a lack of evidence regarding the best maintenance antithrombotic strategy in patients with high-risk AF and stable CAD, particularly as long-term dual therapy with an oral anticoagulant and an antiplatelet drug may increase the risk of bleeding. In the EPIC-CAD trial, we were able to show that edoxaban monotherapy resulted in fewer net adverse clinical events compared with dual antithrombotic therapy in the 12 months after randomization, with less clinically important bleeding and no increase in major ischaemic events."
Dr. Gi-Byoung Nam, study presenter, Asan Medical Center, Seoul, Republic of Korea
The EPIC-CAD trial was an investigator-initiated, open-label, adjudicator-masked, randomized trial. Eligible patients had high-risk AF (CHA2DS2-VASc score ≥2) and stable CAD (if prior revascularisation: after ≥12 months for acute coronary syndrome and after ≥6 months for chronic angina). Patients were randomly assigned in a 1:1 ratio to either monotherapy of standard-dose edoxaban (60 mg once daily or 30 mg once daily with dose-reduction criteria) or dual antithrombotic therapy of standard-dose edoxaban plus a single antiplatelet agent (either aspirin or clopidogrel).
The primary endpoint was the net composite outcome of death from any cause, stroke, systemic embolism, myocardial infarction, unplanned revascularisation, and major or clinically relevant non-major bleeding at 1 year after randomization. Key secondary endpoints included the individual components of the primary endpoint, a composite of major ischaemic events (death, myocardial infarction, ischaemic stroke and systemic embolism), and a composite of major and clinically relevant non-major bleeding.
In total, 1,040 patients were randomized from 18 major cardiac centers in South Korea. The mean age was 72 years and 23% were women. The mean CHA2DS2-VASc score was 4.3. The mean HAS-BLED score was 2.1, indicating a moderate risk of bleeding. Two-thirds had undergone previous revascularisation (66%) and the median time from last revascularisation was 53 months. Patients in the dual antithrombotic therapy group more often received aspirin (62%) than clopidogrel (38%).
In the 12 months after randomization, edoxaban monotherapy significantly reduced the risk of the primary endpoint by 56% compared with dual antithrombotic therapy (6.8% vs. 16.2%; hazard ratio [HR] 0.44; 95% confidence interval [CI] 0.30−0.65; p<0.001). This difference was mainly driven by a 66% reduction in the risk of major bleeding or clinically relevant non-major bleeding with edoxaban monotherapy vs. dual-antithrombotic therapy (4.7% and 14.2%, respectively; HR 0.34; 95% CI 0.22−0.53). The rates of major ischaemic events were 1.6% in the edoxaban monotherapy and 1.8% in the dual-antithrombotic therapy groups (HR 1.23; 95% CI 0.48−3.10). There was no difference in the rate of all-cause mortality in the edoxaban monotherapy and dual-antithrombotic therapy groups (0.6% and 0.7%, respectively; HR 1.29; 95% CI 0.29−5.76).
"Our results are similar with the AFIRE trial in patients with AF and stable CAD, which showed that rivaroxaban monotherapy was non-inferior to dual therapy for efficacy and superior for safety.2 EPIC-CAD used a globally approved dosing regimen. EPIC-CAD provides additional new evidence on the appropriate antithrombotic strategy with standard-dose edoxaban to guide the treatment of patients with AF and stable CAD," concluded Principal Investigator, Professor Duk-Woo Park of the Asan Medical Center, Seoul, Republic of Korea.
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