Asundexian Is Not Approved and Cannot Be Prescribed Outside Clinical Trials
Asundexian is not an FDA-approved anticoagulant for stroke prevention in atrial fibrillation and cannot be prescribed outside of clinical trials. The drug's pivotal phase 3 trial (OCEANIC-AF) was prematurely terminated in 2025 due to inferior efficacy compared to apixaban, with asundexian showing a nearly 4-fold higher rate of stroke or systemic embolism 1.
Clinical Trial Results Demonstrating Inefficacy
The OCEANIC-AF trial randomized 14,810 patients with atrial fibrillation to receive either asundexian 50 mg once daily or standard-dose apixaban 1. The trial was stopped early by the independent data monitoring committee after demonstrating:
- Stroke or systemic embolism occurred in 1.3% of asundexian patients versus 0.4% of apixaban patients (hazard ratio 3.79,95% CI 2.46-5.83) 1
- While major bleeding was lower with asundexian (0.2% vs 0.7%, HR 0.32), this safety benefit was completely overshadowed by the unacceptable increase in thromboembolic events 1
- The trial population had a mean age of 73.9 years, mean CHA2DS2-VASc score of 4.3, and 18.2% had prior stroke or TIA—representing a high-risk population where stroke prevention is critical 1
Mechanism and Rationale for Development
Asundexian is an oral Factor XIa inhibitor that targets the intrinsic coagulation pathway, theoretically allowing anticoagulation with reduced bleeding risk compared to direct oral anticoagulants (DOACs) 2, 3. Phase 2 data from PACIFIC-AF showed:
- 20 mg once daily achieved 81% FXIa inhibition at trough and 90% at peak concentrations 4
- 50 mg once daily achieved 92% FXIa inhibition at trough and 94% at peak concentrations 4
- Bleeding rates appeared lower than apixaban in the phase 2 trial (incidence proportion ratio 0.16 for asundexian 50 mg vs apixaban) 4
However, the phase 3 trial definitively demonstrated that reduced bleeding does not compensate for inadequate stroke prevention 1.
Current FDA-Approved Alternatives
For stroke prevention in atrial fibrillation, the following anticoagulants have FDA approval and guideline support:
Direct Oral Anticoagulants (Preferred)
- Apixaban 5 mg twice daily (2.5 mg twice daily if ≥2 of: age ≥80, weight ≤60 kg, creatinine ≥1.5 mg/dL) 5
- Dabigatran 150 mg twice daily (75 mg twice daily if CrCl 15-30 mL/min) 5
- Rivaroxaban 20 mg once daily (15 mg once daily if CrCl 15-50 mL/min) 5
- Edoxaban 60 mg once daily (30 mg once daily if CrCl 15-50 mL/min, weight ≤60 kg, or certain P-gp inhibitors) 5
The 2019 AHA/ACC/HRS guidelines give a Class 2a, Level of Evidence B-R recommendation that NOACs are preferred over warfarin in NOAC-eligible patients (except those with moderate-to-severe mitral stenosis or mechanical heart valves) 5.
Warfarin (Alternative)
- Warfarin with target INR 2.0-3.0 remains a Class 1, Level of Evidence A recommendation, particularly for patients with mechanical valves or moderate-to-severe mitral stenosis 5
Ongoing Research Context
While asundexian failed in OCEANIC-AF, another phase 3 trial (OCEANIC-AFINA) is planned to evaluate asundexian versus placebo in patients with atrial fibrillation deemed ineligible for standard anticoagulation due to bleeding concerns 2. Additionally, the OCEANIC-STROKE trial is ongoing for secondary stroke prevention 6. However, none of these trials change the current regulatory status—asundexian remains investigational and unavailable for clinical use 2, 3.
Critical Clinical Pitfall
The most important takeaway is that Factor XIa inhibition, despite its theoretical bleeding advantage, proved inadequate for stroke prevention in the highest-quality evidence available 1. This underscores that anticoagulation efficacy cannot be sacrificed for bleeding reduction in high-risk atrial fibrillation patients. Clinicians should prescribe FDA-approved DOACs or warfarin according to established guidelines 5.