Dr. Mustafa Candemir

Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease

ESC 2024
Link: FULL TEXT
https://www.nejm.org/doi/full/10.1056/NEJMoa2407362

Background
Despite consistent guidance from clinical recommendations, there is still a lack of randomized trial data on long-term antithrombotic treatment strategies for patients with atrial fibrillation and stable coronary artery disease.

Methods
We conducted a multicenter, open-label, randomized study with masked adjudicators to evaluate and compare the effects of edoxaban monotherapy versus dual antithrombotic therapy (edoxaban combined with a single antiplatelet agent) in patients who have atrial fibrillation and stable coronary artery disease. This stable CAD was previously treated either through revascularization or managed with medication. Stroke risk was determined using the CHA2DS2-VASc score, which ranges from 0 to 9, with higher scores indicating an increased stroke risk. The primary endpoint was a composite measure including all-cause mortality, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and both major and clinically relevant non-major bleeding at the 12-month mark. Secondary outcomes were a composite of major ischemic events and the incidence of major or clinically relevant non-major bleeding.

Results
The study included 524 patients in the edoxaban monotherapy group and 516 patients in the dual antithrombotic therapy group, with the trial conducted across 18 centers in South Korea. The participants had a mean age of 72.1 years, with 22.9% being women and an average CHA2DS2-VASc score of 4.3. Over 12 months, 34 patients (6.8% based on Kaplan-Meier estimates) in the edoxaban monotherapy group experienced a primary outcome event, compared to 79 patients (16.2%) in the dual antithrombotic therapy group (hazard ratio of 0.44; 95% confidence interval [CI], 0.30 to 0.65; P<0.001). The incidence of major ischemic events over the same period was comparable between the groups. Major or clinically relevant non-major bleeding was observed in 23 patients (4.7% based on Kaplan-Meier estimates) in the edoxaban monotherapy group, versus 70 patients (14.2%) in the dual antithrombotic therapy group (hazard ratio of 0.34; 95% CI, 0.22 to 0.53).

Conclusions
In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy was associated with a significantly lower risk of experiencing a composite of death, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major and clinically relevant non-major bleeding compared to dual antithrombotic therapy over a 12-month period.

Comment

Among patients with atrial fibrillation and chronic coronary artery disease, the use of edoxaban alone showed advantages. Compared to the combination of edoxaban and an antiplatelet agent, edoxaban monotherapy was associated with fewer major adverse cardiac and bleeding events. Notably, the incidence of major ischemic events was comparable between the two treatment regimens. The primary benefit of edoxaban monotherapy stemmed from a significant reduction in major bleeding compared to the combination therapy with edoxaban and an antiplatelet agent. These findings are consistent with those from the AFIRE trial, which evaluated rivaroxaban monotherapy against rivaroxaban combined with an antiplatelet agent. However, it is important to note that both studies were conducted exclusively in Asian populations, which may affect the broader applicability of the results.