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OCEANIC-AF

Asundexian versus Apixaban in Patients with Atrial Fibrillation

Year of Publication: 2025

Authors: Piccini JP, Patel MR, Steffel J, ..., Caso V

Journal: New England Journal of Medicine

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.

Link: https://www.nejm.org/doi/10.1056/NEJMoa2407105

PDF: https://www.researchgate.net/publication...hizbrqMdX2z.1Yk

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?

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 for futility.

        Major Points
        Asundexian is an oral Factor XIa inhibitor designed to reduce thromboembolic events with less bleeding risk.
The trial enrolled 14,810 patients with atrial fibrillation and elevated stroke risk.
Asundexian was associated with a higher rate of stroke/systemic embolism than apixaban (HR 3.79).
Major bleeding occurred significantly less often with asundexian than apixaban (HR 0.32).
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 (e.g., age ≥70, prior stroke/TIA, CKD, etc.)

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

Baseline Characteristics

Characteristic	Control	Active
Age — yr	73.9±7.7	73.9±7.7
Female sex — %	34.6%	35.8%
Hypertension — %	88.8%	88.4%
Diabetes mellitus — %	37.2%	36.7%
Stroke or TIA — %	17.6%	18.7%

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)