Net Clinical Benefit of Edoxaban Versus Apixaban in Patients With Atrial Fibrillation and Coronary Artery Disease

NCT07753200 | Recruiting Phase 4 DMC

• 1 other identifier: SMC 2026-05-061
• Study Type: interventional
• Target: 3,000
• Locations: 1 country
• Sites: 1

Brief Summary

Non-vitamin K antagonist oral anticoagulants (NOACs) have become the standard of care for the prevention of thromboembolic events in patients with AF. In patients with AF and concomitant CAD, the choice of oral anticoagulant is particularly important because clinicians must balance the risks of thromboembolism, coronary ischemic events, as well as bleeding. Among available NOACs, apixaban and edoxaban share a common mechanism of factor Xa inhibition but differ substantially in dosing regimen, pharmacokinetic profile, and degree of renal elimination. In the recent COBRRA trial, apixaban was associated with significantly lower clinically relevant bleeding compared with rivaroxaban in patients with acute venous thromboembolism, without compromising efficacy against recurrent thromboembolism. Although these data support apixaban as an important benchmark NOAC, direct randomized comparisons between edoxaban and apixaban are lacking, particularly in patients with AF and coexisting CAD. Once-daily dosing and lower renal elimination fraction of edoxaban may offer practical advantages, particularly in elderly patients or those with impaired renal function, by potentially improving adherence and simplifying dose adjustment. Whether these pharmacological differences translate into meaningful differences in overall clinical outcomes remains uncertain. Given that anticoagulation strategies inherently require balancing thromboembolic protection against bleeding risk, evaluation using a net clinical outcome is clinically most relevant. Therefore, this randomized controlled trial is designed to determine whether edoxaban-based therapy is non-inferior to apixaban with respect to NACE, a composite of death, thromboembolic, and major bleeding outcomes in patients with AF and concomitant CAD.

Conditions

Patients With Atrial Fibrillation and Cornary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Net Adverse Clinical Events (NACE)

  A composite of death from any causes, Myocardial Infarction, Stroke, systemic embolic events or International Society on Thrombsis and Hemostasis major beeling

  5 years

Secondary Outcomes (1)

• Major Adverse Cardiovascular and Cerebrovascular Events (MACEE)

  5 years

Study Arms (2)

Edoxaban-based treatment group

EXPERIMENTAL

Edoxaban 60mg once daily orally, continue until follow-up is complete.

Drug: Edoxaban

Apixaban-based treatment group

ACTIVE COMPARATOR

Apixaban 5mg twice a day orally, continue until follow-up is complete.

Drug: Apixaban

Interventions

Edoxaban DRUG

Edoxaban 60mg will be administered once daily orally according to the study protocol.

Edoxaban-based treatment group

Apixaban DRUG

Apixaban 5mg will be administered twice a day orally according to the study protocol.

Apixaban-based treatment group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• i) Patients must be at least 19 years of age ii) Patients with AF requiring oral anticoagulation therapy (CHA2DS2-VaSc 2 or more) iii) Documented coronary artery disease, defined as at least one of the following:
• history of percutaneous coronary intervention (PCI)
• history of coronary artery bypass grafting (CABG)
• major epicardial coronary artery stenosis ≥50% on coronary computed tomography angiography (CCTA) or invasive coronary angiography iv) Patients who can understand risks, benefits and treatment alternatives and sign informed consent voluntarily.

You may not qualify if:

• i) Known hypersensitivity or contraindications to study medications (apixaban or edoxaban) ii) Severe renal impairment (creatinine clearance \<15 mL/min) or dialysis iii) Active major bleeding iv) Indication requiring alternative anticoagulation (e.g., mechanical valve surgery or moderate / severe mitral stenosis) v) Non-cardiac co-morbid conditions are present with life expectancy \<1 year or that may result in protocol non-compliance (per site investigator's medical judgment) vi) Pregnant or lactating women

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

MeSH Terms

Interventions

edoxaban; apixaban

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 31, 2026
• First Posted: August 7, 2026
• Study Start: July 20, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): December 31, 2031
• Last Updated: August 7, 2026

Record last verified: 2026-07

Locations

KR (1)