- Question
- To determine whether asundexian, an oral factor XIa inhibitor, is at least noninferior to apixaban for preventing stroke or systemic embolism in patients with atrial fibrillation, with less major bleeding.
- Design
- Phase 3, international, randomized 1:1, double-blind, active-controlled trial including 14810 patients in the intention-to-treat population. It was stopped prematurely at the recommendation of the independent data monitoring committee.
- Population
- Patients with atrial fibrillation at high risk of stroke: mean age 73.9 years, 35.2% women, 18.6% with chronic kidney disease, 18.2% with prior stroke or TIA, and mean CHA2DS2-VASc score of 4.3.
- Intervention
- Asundexian 50 mg once daily.
- Control
- Standard-dose apixaban.
- Primary outcome
- Efficacy: stroke or systemic embolism, testing noninferiority of asundexian versus apixaban. Safety: major bleeding, testing superiority of asundexian.
- Results
- Stroke or systemic embolism occurred in 98 patients (1.3%) with asundexian and in 26 (0.4%) with apixaban (HR 3.79; 95% CI 2.46 to 5.83). Major bleeding occurred in 17 patients (0.2%) with asundexian and in 53 (0.7%) with apixaban (HR 0.32; 95% CI 0.18 to 0.55).
- Safety
- There were fewer major bleeding events with asundexian than with apixaban. The incidence of any adverse event appeared similar in the two groups.
- Conclusion
- Asundexian 50 mg daily was associated with a higher incidence of stroke or systemic embolism than apixaban before the trial was stopped early, with less major bleeding.
- Why it matters
- It showed that factor XIa inhibition at this dose failed to match the efficacy of a standard direct oral anticoagulant in atrial fibrillation despite lower bleeding risk, and shaped the subsequent development of this drug class.
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 14, 2026