OCEANIC-AF
Asundexian versus Apixaban in Patients with Atrial Fibrillation
Clinical Question
Does the oral Factor XIa inhibitor asundexian prevent stroke or systemic embolism in patients with atrial fibrillation as effectively as apixaban, with less bleeding?
Study Overview
Objective
Is asundexian, an oral factor XIa inhibitor, noninferior to apixaban for preventing stroke or systemic embolism in patients with Afib, and superior in reducing major bleeding.
Study Summary
The trial was prematurely stopped due to higher stroke/systemic embolism rates with asundexian versus apixaban
Intervention
Asundexian 50 mg once daily vs. standard-dose apixaban (5 mg BID or 2.5 mg BID for dose-reduction criteria).
Patients per Arm
Asundexian: 7415, Apixaban: 7395
Bottom Line
In patients with atrial fibrillation, asundexian 50 mg daily led to a higher risk of stroke or systemic embolism compared with apixaban, but reduced major bleeding; the trial was stopped early due to excess stroke or systemic embolism in the asundexian group.
Major Points
- Asundexian is an oral Factor XIa inhibitor designed to reduce thromboembolic events with less bleeding risk.
- A total of 16,436 patients were screened, 14,830 were randomly assigned, and 14,810 (7415 asundexian, 7395 apixaban) formed the intention-to-treat population.
- Asundexian was associated with a higher rate of stroke/systemic embolism than apixaban (HR 3.79).
- Major bleeding occurred less often with asundexian than apixaban (17 [0.2%] vs. 53 [0.7%]; HR 0.32); however, no formal significance testing was performed owing to early termination of the trial.
- The trial was terminated early due to a clear difference in efficacy favoring apixaban.
- Despite reduced bleeding, asundexian failed to demonstrate noninferiority for efficacy.
Design
Study Type: Randomized, double-blind, active-controlled, event-driven trial
Randomization: 1
Blinding: Double-blind, double-dummy
Enrollment Period: December 2022 – November 2023
Follow-up Duration: Median 155 days
Centers: 1035
Countries: 38 countries
Sample Size: 14810
Analysis: Intention-to-treat; stratified cause-specific Cox regression; SAS v9.4
Inclusion Criteria
- Age ≥18 years
- Documented atrial fibrillation (within 12 months)
- CHA2DS2-VASc score ≥3 in men or ≥4 in women
- Or CHA2DS2-VASc score of 2 in men or 3 in women with ≥1 additional risk factor (age ≥70; prior stroke/TIA/systemic embolism; eGFR <50; previous nontraumatic major bleeding; planned single-agent antiplatelet therapy ≥6 months; or no more than 6 consecutive weeks of oral anticoagulant treatment before randomization)
Exclusion Criteria
- Mechanical heart valve or moderate-to-severe mitral stenosis
- Indication for anticoagulation other than atrial fibrillation
- Estimated GFR <15 mL/min/1.73m²
- Major bleeding or stroke within the past 14 days
- Concomitant need for long-term dual antiplatelet therapy
Arms
| Field | Asundexian | Control |
|---|---|---|
| Intervention | Asundexian 50 mg once daily plus placebo matching apixaban | Apixaban 5 mg twice daily (2.5 mg if dose reduction criteria met) plus placebo matching asundexian |
| Duration | Median 155 days | Median 155 days |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Stroke or systemic embolism (intention-to-treat population) | Primary | 0.4% (26 patients); 1.02 events/100 person-years | 1.3% (98 patients); 3.85 events/100 person-years | 3.79 | not formally tested due to early termination |
| Major bleeding | Secondary | 0.7% (53 patients); 1.93 events/100 person-years | 0.2% (17 patients); 0.62 events/100 person-years | 0.32 | not formally tested |
| Intracranial hemorrhage | Secondary | 0.2% (18 patients) | <0.1% (3 patients) | 0.16 | not formally tested |
| Major bleeding | Adverse | 0.7% | 0.2% | 0.32 | not formally tested |
| Intracranial hemorrhage | Adverse | 0.2% | <0.1% | 0.16 | not formally tested |
| Any adverse event | Adverse | 34.9% | 34.9% |
Subgroup Analysis
No subgroups demonstrated superior efficacy for asundexian; bleeding reduction was consistent across subgroups
Criticisms
- Trial was stopped early due to excess thromboembolic events in the asundexian arm
- Short median follow-up (155 days) limits long-term conclusions
- Only one dose of asundexian was tested; optimal dosing is uncertain
- Event rates lower than expected in the apixaban arm, affecting power
Funding
Bayer
Based on: OCEANIC-AF (New England Journal of Medicine, 2025)
Authors: Piccini JP, Patel MR, Steffel J, ..., Caso V
Citation: Piccini JP, Patel MR, Steffel J, et al. Asundexian versus Apixaban in Patients with Atrial Fibrillation. N Engl J Med. 2025;392:23–32.
Content summarized and formatted by NeuroTrials.ai.