For AF With Stable CAD, Edoxaban Alone Prevents More Adverse Outcomes Than Edoxaban Plus an Antiplatelet Agent

In patients with atrial fibrillation (AF) and stable coronary artery disease (CAD), does edoxaban (Savaysa) alone prevent more adverse outcomes than edoxaban plus an antiplatelet agent?

For patients with AF and stable CAD, edoxaban monotherapy prevents more adverse outcomes (mostly fewer major bleeding events) than edoxaban plus an antiplatelet agent. The net benefit is less clear for women than for men. (Level of Evidence = 1b)

Based on randomized trials of patients with AF who experienced an acute episode of unstable angina, initial therapy with a direct oral anticoagulant plus a P2Y₁₂ inhibitor is recommended for 6 to 12 months, followed by a direct oral anticoagulant alone. This study randomized 1,040 Korean adults with prevalent (45%) or paroxysmal (55%) AF; stable CAD; and a CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥ 75 [doubled], diabetes, stroke [doubled], vascular disease, age 65 to 74, sex [female]) score of 2 or greater, indicating a moderate or worse risk of stroke. Stable CAD was defined as heart disease treated with percutaneous coronary intervention or bypass surgery at least 6 months earlier, an acute coronary syndrome treated with percutaneous coronary intervention or bypass at least 12 months earlier, or at least 50% stenosis of at least one coronary artery on angiogram. People at high risk of bleeding, those with a history of liver or kidney dysfunction, or a history of intracerebral hemorrhage were excluded.

At baseline, groups were balanced with a mean age of 72 years—77% were men, 8% had a history of bypass surgery, and the average CHA₂DS₂-VASc score was 4.3. Analysis was by intention to treat. Participants were randomized to receive edoxaban, 60 mg, plus placebo or edoxaban, 60 mg, plus low-dose aspirin (62%) or clopidogrel (38%) at the discretion of the treating physician. The primary outcome was a composite of vascular events (ie, death, myocardial infarction, stroke, systemic embolization, or unplanned revascularization) and major or clinically relevant nonmajor bleeding events. After 12 months of follow-up, the primary outcome was significantly less likely in the edoxaban monotherapy group (6.8% vs 16.2%; hazard ratio [HR] = 0.44; 95% CI, 0.30–0.65; number needed to treat [NNT] = 11). The differences between groups for individual vascular outcomes were not statistically significant, and vascular events were uncommon (eg, 15 vs 11 ischemic events), but they all trended toward fewer events with monotherapy. Most of the net benefit was driven by fewer major or clinically relevant nonmajor bleeding events with monotherapy (4.7% vs 14.2%; HR = 0.32; 95% CI, 0.14–0.73; NNT = 10). In subgroup analyses, the reduction in the primary composite outcome was greater for men (HR = 0.37; 95% CI, 0.23–0.58) than for women (HR = 0.81; 95% CI, 0.39–1.72).

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry and foundation

Allocation: Concealed

Setting: Outpatient (any)

Reference: Cho MS, Kang DY, Ahn JM, et al.; EPIC-CAD Investigators. Edoxaban antithrombotic therapy for atrial fibrillation and stable coronary artery disease. N Engl J Med. 2024;391(22):2075-2086.

Editor’s Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.