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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

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 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

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)

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.

OCEANIC-AF

(2025)

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).

Inclusion Criteria

Adults with atrial fibrillation and CHA₂DS₂-VASc ≥3 (men) or ≥4 (women), or ≥2/3 with additional stroke risk factors; no more than 6 weeks of prior anticoagulant use.

Study Design

Arms: Asundexian vs. Apixaban

Patients per Arm: Asundexian: 7415, Apixaban: 7395

Outcome

• Primary efficacy: Stroke/systemic embolism – Asundexian 1.3%, Apixaban 0.4% (HR 3.79). • Primary safety: ISTH major bleeding – Asundexian 0.2%, Apixaban 0.7% (HR 0.32). • All-cause death: Asundexian 0.8%, Apixaban 1.0%. • ISTH major or CRNM bleeding: Asundexian 1.1%, Apixaban 2.6%. • Intracranial hemorrhage: Asundexian <0.1%, Apixaban 0.2%. • Net clinical benefit (stroke, systemic embolism, or major bleeding): Worse with asundexian (1.6% vs. 1.0%, HR 1.61).

Bottom Line

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.

Study Design

Study Type: Randomized, double-blind, active-controlled, event-driven trial
Randomization: Yes
Blinding: Double-blind, double-dummy
Sample Size: 14810
Follow-up: Median 155 days
Centers: 1035
Countries: 38 countries

Primary Outcome

Definition: Stroke or systemic embolism (intention-to-treat population)

Control	Intervention	HR/OR	P-value
0.4% (26 patients); 1.02 events/100 person-years	1.3% (98 patients); 3.85 events/100 person-years	3.79 (2.46–5.83)	not formally tested due to early termination

Limitations & 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

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.

View Original Publication →

OCEANIC-AF

Asundexian versus Apixaban in Patients with Atrial Fibrillation

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

Ask about OCEANIC-AF