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OCEANIC-STROKE

Oral Factor Eleven A Inhibitor Asundexian as Novel Antithrombotic Stroke

Year of Publication: 2026

Authors: M. Sharma, Q. Dong, T. Hirano, ..., A. Shoamanesh

Journal: New England Journal of Medicine

Citation: N Engl J Med 2026;394:1467-79

Clinical Question

In patients with recent noncardioembolic ischemic stroke or high-risk TIA on antiplatelet therapy, does asundexian 50 mg once daily (an activated factor XI inhibitor) reduce the risk of recurrent stroke compared with placebo?

Bottom Line

Among patients with noncardioembolic ischemic stroke or high-risk TIA treated with antiplatelet therapy, asundexian at 50 mg daily resulted in lower risks of ischemic stroke and major cardiovascular events than placebo, without a higher risk of major bleeding

        Major Points
        First successful factor XIa inhibitor trial for secondary stroke prevention
12,327 patients randomized across 702 centers in 37 countries
26% relative reduction in ischemic stroke (absolute difference 2.2%)
17% reduction in composite of CV death, MI, or stroke
No increase in major bleeding, validating thrombosis-hemostasis uncoupling concept
Consistent benefit across stroke subtypes including small-vessel occlusion
Included patients treated with thrombolysis and thrombectomy
Median follow-up 567 days (19 months)

      

Design

Study Type: Phase 3 randomized controlled trial

Randomization: 1

Blinding: Double-blind, placebo-controlled with interactive Web-based randomization system

Enrollment Period: January 2023 to February 2025

Follow-up Duration: Median 567 days (IQR 377-729), event-driven trial

Centers: 702

Countries: 37 countries across North America, South America, Europe, Australia, Israel, Asia-Pacific

Sample Size: 12327

Analysis: Intention-to-treat with Aalen-Johansen estimates treating death as competing event; cause-specific Cox proportional-hazards regression; hierarchical testing for multiplicity control

Inclusion Criteria

Age ≥18 years
Noncardioembolic ischemic stroke or high-risk TIA within 72 hours of symptom onset
Ischemic stroke: NIHSS score ≤15
High-risk TIA: ABCD2 score 6-7
Plan for dual or single antiplatelet therapy
At least one of: nonlacunar infarct on imaging, history of atherosclerosis (CAD, PVD, or carotid stenosis ≥50%), or imaging evidence of cerebrovascular atherosclerosis
If treated with IV thrombolysis or thrombectomy, ≥24 hours elapsed since treatment

Exclusion Criteria

History of atrial fibrillation or other indication for anticoagulation
Active nontrivial bleeding including parenchymal hematoma on imaging
Qualifying stroke related to procedure or specific cause (e.g., bacterial endocarditis)

Arms

Field	Asundexian Group	Control
Intervention	Asundexian 50 mg orally once daily added to planned dual or single antiplatelet therapy, started within 4 hours of randomization and within 72 hours of symptom onset	Matching placebo orally once daily added to planned dual or single antiplatelet therapy, started within 4 hours of randomization and within 72 hours of symptom onset
Duration	Median 567 days follow-up	Median 567 days follow-up

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
First occurrence of ischemic stroke (new focal neurologic deficit lasting ≥24 hours or with imaging evidence of infarction)	Primary	518 (8.4%); 6.0 events/100 patient-years; 7.0% at 1 year	384 (6.2%); 4.4 events/100 patient-years; 5.1% at 1 year	0.74	<0.001
Any stroke (ischemic or hemorrhagic)	Secondary	545 (8.8%); 7.3% at 1 year	404 (6.6%); 5.3% at 1 year	0.74 (0.65-0.84)	<0.001
Death from CV causes, MI, or stroke	Secondary	685 (11.1%); 9.0% at 1 year	568 (9.2%); 7.3% at 1 year	0.83 (0.74-0.92)	<0.001
Death from any cause, MI, or stroke	Secondary	757 (12.3%); 9.7% at 1 year	649 (10.5%); 8.3% at 1 year	0.85 (0.77-0.95)	0.003
Ischemic stroke in first 90 days	Secondary	218 (3.5%)	183 (3.0%)	0.84 (0.69-1.02)	0.08
Disabling or fatal stroke	Secondary	185 (3.0%); 2.5% at 1 year	128 (2.1%); 1.7% at 1 year	0.69 (0.55-0.87)	Not tested (hierarchical)
Death from any cause	Secondary	253 (4.1%)	248 (4.0%)	0.98 (0.83-1.17)	Not tested
ISTH major bleeding	Adverse	107 (1.7%); 1.6% at 1 year	117 (1.9%); 1.6% at 1 year	1.10 (0.85-1.44)	0.46
Major or clinically relevant nonmajor bleeding	Adverse	307 (5.0%); 4.4% at 1 year	339 (5.5%); 4.8% at 1 year	1.12 (0.96-1.30)	0.16
Symptomatic intracranial hemorrhage	Adverse	36 (0.6%)	41 (0.7%)	1.15 (0.74-1.80)
Hemorrhagic stroke	Adverse	20 (0.3%)	13 (0.2%)	0.66 (0.33-1.32)
Fatal bleeding	Adverse	8 (0.1%)	14 (0.2%)	1.77 (0.74-4.23)
Any adverse event	Adverse	70.1%	69.3%
Serious adverse events	Adverse	1196 (19.5%)	1177 (19.2%)

Subgroup Analysis

Effects mostly consistent across subgroups including age, sex, geographic region, race, stroke subtype, time to treatment, reperfusion therapy status, NIHSS score, and planned antiplatelet therapy. Notable: Black patients only 2.3% (HR 0.28, wide CI)

Criticisms

Relatively few patients with severe stroke (NIHSS ≥8)
Low enrollment of high-risk TIA patients (only 5%)
Small percentage of Black patients (2.3%), limiting generalizability
26% discontinuation rate in both groups
No significant benefit for early (90-day) ischemic stroke endpoint
Median follow-up only 19 months, long-term safety unknown
Industry-sponsored trial with potential bias
Excluded patients with atrial fibrillation or anticoagulation indication
Limited data on combined use with newer P2Y12 inhibitors beyond clopidogrel

Funding

Bayer (sponsor of the trial)

Based on: OCEANIC-STROKE (New England Journal of Medicine, 2026)

Authors: M. Sharma, Q. Dong, T. Hirano, ..., A. Shoamanesh

Citation: N Engl J Med 2026;394:1467-79

Content summarized and formatted by NeuroTrials.ai.

OCEANIC-STROKE

(2026)

Objective

To evaluate the efficacy and safety of asundexian, an activated factor XI inhibitor, for secondary stroke prevention in patients with noncardioembolic ischemic stroke or high-risk TIA

Study Summary

• Asundexian reduced ischemic stroke by 26% (6.2% vs 8.4%, HR 0.74, P<0.001)
• No increase in major bleeding (1.9% vs 1.7%, HR 1.10)
• First successful factor XIa inhibitor trial demonstrating thrombosis-hemostasis uncoupling

Intervention

Asundexian 50 mg once daily versus placebo, added to antiplatelet therapy (dual or single), started within 72 hours of symptom onset

Inclusion Criteria

Adults ≥18 years with noncardioembolic ischemic stroke (NIHSS ≤15) or high-risk TIA (ABCD2 6-7) within 72 hours, plus evidence of atherosclerosis or nonlacunar infarct

Study Design

Arms: Asundexian 50 mg daily vs Placebo, both with antiplatelet therapy

Patients per Arm: 6162 asundexian, 6165 placebo (12,327 total)

Outcome

• Primary: 26% relative reduction in ischemic stroke (6.2% vs 8.4%, HR 0.74, 95% CI 0.65-0.84, P<0.001)
• Key secondary: 17% reduction in CV death/MI/stroke (9.2% vs 11.1%, HR 0.83, P<0.001)
• Safety: No increase in major bleeding (1.9% vs 1.7%, HR 1.10)

Clinical Question

Whether the addition of asundexian, an activated factor XI inhibitor, to antiplatelet therapy would be superior to antiplatelet therapy alone for the secondary prevention of ischemic stroke in patients with noncardioembolic stroke or high-risk TIA?

Bottom Line

Major Points

First successful factor XIa inhibitor trial for secondary stroke prevention
12,327 patients randomized across 702 centers in 37 countries
26% relative reduction in ischemic stroke (absolute difference 2.2%)
17% reduction in composite of CV death, MI, or stroke
No increase in major bleeding, validating thrombosis-hemostasis uncoupling concept
Consistent benefit across stroke subtypes including small-vessel occlusion
Included patients treated with thrombolysis and thrombectomy
Median follow-up 567 days (19 months)

Study Design

Study Type: Phase 3 randomized controlled trial
Randomization: Yes
Blinding: Double-blind, placebo-controlled with interactive Web-based randomization system
Sample Size: 12327
Follow-up: Median 567 days (IQR 377-729), event-driven trial
Centers: 702
Countries: 37 countries across North America, South America, Europe, Australia, Israel, Asia-Pacific

Primary Outcome

Definition: First occurrence of ischemic stroke (new focal neurologic deficit lasting ≥24 hours or with imaging evidence of infarction)

Control	Intervention	HR/OR	P-value
518 (8.4%); 6.0 events/100 patient-years; 7.0% at 1 year	384 (6.2%); 4.4 events/100 patient-years; 5.1% at 1 year	0.74 (0.65 to 0.84)	<0.001

Limitations & Criticisms

Relatively few patients with severe stroke (NIHSS ≥8)
Low enrollment of high-risk TIA patients (only 5%)
Small percentage of Black patients (2.3%), limiting generalizability
26% discontinuation rate in both groups
No significant benefit for early (90-day) ischemic stroke endpoint
Median follow-up only 19 months, long-term safety unknown
Industry-sponsored trial with potential bias
Excluded patients with atrial fibrillation or anticoagulation indication
Limited data on combined use with newer P2Y12 inhibitors beyond clopidogrel

Citation

N Engl J Med 2026;394:1467-79

View Original Publication →

OCEANIC-STROKE

Oral Factor Eleven A Inhibitor Asundexian as Novel Antithrombotic Stroke

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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