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September 5, 2026EP EuropaceOpen Access

Edoxaban Antithrombotic Therapy in Diabetic Patients with Atrial Fibrillation and Stable Coronary Artery Disease: The EPIC-CAD Trial

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Why the study?

Does edoxaban monotherapy reduce adverse clinical and bleeding events compared to dual antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease?

Population

1040 patients with atrial fibrillation and stable coronary artery disease, including 421 with diabetes.

Comparison

Edoxaban monotherapy vs Dual antithrombotic therapy

Design

RCT, randomized

Follow-up

12 months

Key result

Edoxaban monotherapy reduced the primary composite outcome compared to dual therapy in both diabetic (6.3% vs 13.7%; HR 0.44) and non-diabetic (6.7% vs 16.3%; HR 0.39) patients with AF and stable CAD.

Authors

SLS C LeeMCMin Soo ChoDKDo‐Yoon Kang

Discussion

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Member takes

Overview

Supports edoxaban monotherapy over dual therapy in AF with stable CAD regardless of diabetes; confirms consistent benefit without interaction in this RCT.

Key Points

  • To determine whether the comparative efficacy and safety of edoxaban monotherapy versus dual antithrombotic therapy differ according to diabetes status in patients with atrial fibrillation and stable coronary artery disease.
  • Randomized clinical trial (EPIC-CAD) comparing edoxaban monotherapy against dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in 1040 patients with atrial fibrillation and stable coronary artery disease, including 421 patients with diabetes.
  • Evaluated a composite primary endpoint of all-cause death, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major or clinically relevant nonmajor bleeding over 12 months.
  • Edoxaban monotherapy significantly reduced the primary composite outcome at 12 months compared to dual therapy in diabetic patients (6.3% vs. 13.7%; HR 0.44; 95% CI 0.23-0.83; P=0.01) and in non-diabetic patients (6.7% vs. 16.3%; HR 0.39; 95% CI 0.23-0.65; P=0.001).
  • Overall incidence of the primary outcome did not differ between diabetic and non-diabetic cohorts (9.7% vs. 11.6%; HR 0.82; 95% CI 0.56-1.20; P=0.30), with no significant interaction by diabetes status (P-for-interaction=0.78).

Study Design

Type

RCT (n=1,040)

Randomization

randomized

Structured PICO

Does edoxaban monotherapy reduce adverse clinical and bleeding events compared to dual antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease?

P
Population
1040 patients with atrial fibrillation and chronic stable coronary artery disease (40.5% with diabetes), followed for 12 months.
I
Intervention
Edoxaban monotherapy
C
Comparator
Dual antithrombotic therapy (edoxaban plus a single antiplatelet agent)
O
Outcome
Composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major or clinically relevant nonmajor bleeding at 12 monthscomposite

Edoxaban monotherapy significantly reduces the risk of a composite of adverse clinical and bleeding events compared to dual antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease, regardless of diabetes status.

Cite This Study

Lee et al. (2026) conducted an RCT in atrial fibrillation and stable coronary artery disease (n=1,040). edoxaban monotherapy vs. dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) was evaluated on composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major or clinically relevant nonmajor bleeding at 12 months. Edoxaban monotherapy reduced the primary composite outcome compared to dual therapy in both diabetic (6.3% vs 13.7%; HR 0.44) and non-diabetic (6.7% vs 16.3%; HR 0.39) patients with AF and stable CAD.

synapsesocial.com/papers/6a9bd4046b95aff0620eb565https://doi.org/10.1093/europace/euag247
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Off-label underdosing of edoxaban antithrombotic therapy for patients with atrial fibrillation and stable coronary artery disease: findings from the EPIC-CAD trial.2025
  2. 2Association of diabetes mellitus status and clinical outcomes of edoxaban in patients with atrial fibrillation: a sub-analysis from the ETNA-AF Asian registry2026
  3. 3Dual antithrombotic therapy using potent antiplatelet inhibitors in atrial fibrillation and acute coronary syndrome: a randomized controlled trial2026
  4. 4Effects of anticoagulation in patients with device-detected atrial fibrillation and multiple stroke risk factors: a win ratio analysis of the NOAH-AFNET 6 trial2025 · 4 citations
  5. 5Impact of Age on Bleeding, Stroke, and Mortality in Edoxaban-Treated Patients with Atrial Fibrillation: Results from the ETAF-TR Registry2026