Arrhythmias & electrophysiology
Off-label underdosing of edoxaban antithrombotic therapy for patients with atrial fibrillation and stable coronary artery disease: findings from the EPIC-CAD trial
Primary result · Composite of death, myocardial infarction, stroke, systemic embolism, unplanned revascularisation and major or clinically relevant non-major bleedingResult — go to the resultAdjusted hazard ratio 0.77 95% CI 0.39–1.54Authors' conclusion
In patients with AF and stable CAD, there was no significant difference in the rate of primary outcome between off-label underdose and standard-dose edoxaban. The benefit of edoxaban monotherapy over dual antithrombotic therapy was consistent regardless of edoxaban underdosing. However, given the analyses were underpowered and the CI was wide, the results cannot be considered clinically directive.
Study context
- Population
- Patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) without dose-reduction criteriapatients (66.7%) without dose-reduction criteria, of the 1040 randomised patients, of whom 121 patients (17.4%) received edoxaban underdosing
- Participants
- 694 patients
- Comparison
- Off-label underdose vs standard-dose edoxaban
- Under-dose edoxabann = 121
- Primary endpoint
- Composite of:
- Death
- Myocardial infarction
- Stroke
- Systemic embolism
- Unplanned revascularisation and major or clinically relevant non-major bleeding
- Follow-up
- 12 months
Methodological detailsanalysis of the EPIC-CAD trial
- Analysis of the EPIC-CAD trial
Primary result
As reported in the abstract
Adjusted hazard ratio
0.77
95% CI 0.39–1.54
By group
Off-label underdose vs standard-dose edoxaban
adjusted HR 0.77 (95% CI 0.39–1.54)
Further findings
Major ischaemic events
| Comparison | Standard-dose edoxaban | Under-dose edoxaban | HR (95% CI) | |
|---|---|---|---|---|
| Standard-dose and under-dose edoxaban groupsDirection not stated in the abstract | 1.4% | 1.7% | 1.14 (0.22–5.91) | |
| 0.20.5125Hazard ratio (log scale) |
Edoxaban monotherapy vs dual antithrombotic therapy, regardless of underdosing
- Edoxaban monotherapy was associated with lower risk of primary net-clinical outcomes and bleeding compared with dual antithrombotic therapy, regardless of edoxaban underdosing
Safety
Major or clinically relevant non-major bleeding
| Comparison | Standard-dose edoxaban | Under-dose edoxaban | HR (95% CI) | |
|---|---|---|---|---|
| Standard-dose and under-dose edoxaban groupsDirection not stated in the abstract | 9.0% | 8.4% | 0.87 (0.42–1.78) | |
| 0.512Hazard ratio (log scale) |
Original publication
Off-label underdosing of edoxaban antithrombotic therapy for patients with atrial fibrillation and stable coronary artery disease: findings from the EPIC-CAD trial. Heart. Published 9 September 2025. doi:10.
Summarised from the published abstract; every number is checked against it