- Question
- Is edoxaban, an oral direct factor Xa inhibitor, noninferior to warfarin for preventing stroke and systemic embolism in patients with atrial fibrillation, and how does it compare on safety?
- Design
- Randomized, double-blind, double-dummy, multicenter, multinational trial in 21105 patients with a median follow-up of 2.8 years, comparing two once-daily edoxaban regimens with warfarin.
- Population
- Patients with atrial fibrillation at moderate-to-high risk.
- Intervention
- Once-daily edoxaban in two regimens: high dose (60 mg) and low dose (30 mg), with warfarin placebo.
- Control
- Warfarin with edoxaban placebo; median time in the therapeutic range was 68.4%.
- Primary outcome
- Composite of stroke or systemic embolism, with each edoxaban regimen tested for noninferiority to warfarin during the treatment period.
- Results
- The annualized primary end point rate was 1.50% with warfarin, 1.18% with high-dose edoxaban (HR 0.79; 97.5% CI 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (HR 1.07; 97.5% CI 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, high-dose edoxaban showed a favorable trend (HR 0.87; 97.5% CI 0.73 to 1.04; P=0.08). Death from cardiovascular causes was lower with both doses (HR 0.86 and 0.85, respectively).
- Safety
- Annualized major bleeding was 3.43% with warfarin, 2.75% with high-dose edoxaban (HR 0.80; 95% CI 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (HR 0.47; 95% CI 0.41 to 0.55; P<0.001).
- Conclusion
- Both once-daily edoxaban regimens were noninferior to warfarin for preventing stroke or systemic embolism and were associated with less bleeding and lower cardiovascular mortality.
- Why it matters
- It established edoxaban as an alternative to warfarin with a lower bleeding risk, broadening the options of direct oral anticoagulants in atrial fibrillation.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 7, 2026