OCEANIC-STROKE: Asundexian Reduces Stroke Risk Without Increasing Bleeding, With Andrew Russman, DO

Asundexian, an investigational oral Factor XIa (FXIa) inhibitor in development by Bayer, has shown its superiority to placebo in preventing ischemic stroke in patients after a non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA), based on results from the pivotal phase 3 OCEANIC-STROKE trial.¹

Despite a variety of treatment options, the risk of secondary stroke remains substantial – roughly 1 in 10 ischemic stroke survivors will experience another within 1 year, and 1 in 5 will have another stroke within 5 years. Secondary strokes are commonly more disabling and are associated with higher mortality and a greater risk of dementia. Combining current strategies can reduce the risk of secondary stroke but has been associated with an increased bleeding risk.²

“I think it’s really important to recognize that we’re always concerned that we’re adding bleeding risk,” Andrew Russman, DO, neurologist and section head of stroke and vascular neurology at the Cleveland Clinic, told HCPLive in an exclusive interview. “But that was not the case with asundexian in this study. Essentially, patients benefited from a reduction in their ischemic stroke risk without a concomitant increase in bleeding risk. And this is critically important.”

OCEANIC-STROKE was a multicenter, international, randomized, placebo-controlled, double-blind, parallel group, event-driven phase 3 study, conducted at 741 locations worldwide. Investigators enrolled patients who were ≥18 years old with acute non-cardioembolic stroke or high-risk TIA and systemic or cerebrovascular atherosclerosis or acute non-lacunar infarct. Patients were excluded if they had ischemic stroke ≤7 days before the index event, a history of atrial fibrillation or flutter, left ventricular thrombus, mechanic valve, or other cardioembolic source of stroke, among other criteria.³

The study’s primary endpoints were time to first occurrence of ischemic stroke and time to first occurrence of International Society on Thrombosis and Hemostasis (ISTH) major bleeding, both up to 31 months. Secondary outcomes included time to first occurrence of ischemic and hemorrhagic strokes, time to first occurrence of a composite of cardiovascular death, myocardial infarction, or stroke, and time to first occurrence of all-cause mortality, among others.³

A total of 12,327 patients were enrolled in the trial; of these, 43% had large-artery atherosclerosis, 23% had small-vessel occlusion, 30% had stroke of undetermined etiology, 3% had other etiology, and 2% had cardioembolic stroke. Patients were randomly assigned in a 1:1 ratio to receive either oral asundexian once daily or matching placebo.^1,3

Russman and colleagues found that asundexian reduced ischemic stroke by 26% (HR, 0.74; 95% CI, 0.65-0.84; P <.0001) with no increase in risk of ISTH major bleeding. This was consistent across all subgroups, including age, sex, index event, stroke subtype, National Institutes of Health Stroke Scale (NIHSS), and acute stroke therapy.¹

Secondary endpoints also showed that asundexian reduced ischemic and hemorrhagic stroke risk by 26% (6.6% vs 8.8%; HR, 0.74; 95% CI, 0.65-0.84; P <.0001) compared to placebo. Additionally, investigators saw no increase in the rate of ISTH major bleeding between asundexian and placebo (1.9% vs 1.7%; HR, 1.1; 95% CI, 0.85-1.44). The risk of bleeding was also similar compared to rates in the placebo arm.¹

“The benefit of the Factor XIa inhibitors is that they’re relatively selective; they act against the bad clot without harming the good clotting that’s part of healing,” Russman told HCPLive. “Anticoagulants in general act against a variety of clotting, whether it’s the kind we need for healing or the bad kind of clotting that’s part of a pathologic process of a clot that could form and travel to the brain and cause a stroke.”

Asundexian has been granted Fast Track Designation by the US Food and Drug Administration (FDA).¹

Editor’s Note: Russman reports disclosures with Genentech, Medtronic, and Boston Scientific Corporation.

References

1. Bayer. Bayer’s asundexian demonstrated a substantial 26% reduction in stroke after a non-cardioembolic ischemic stroke or high-risk transient ischemic attack, with no increase in ISTH major bleeding versus placebo. BusinessWire. February 5, 2026. Accessed February 5, 2026. https://www.businesswire.com/news/home/20260205888712/en/Bayers-Asundexian-Demonstrated-a-Substantial-26-Reduction-in-Stroke-After-a-Non-Cardioembolic-Ischemic-Stroke-or-High-Risk-Transient-Ischemic-Attack-With-No-Increase-in-ISTH-Major-Bleeding-Versus-Placebo

2. Sharma M. Factor XIa Inhibition With Asundexian in Acute Non-Cardioembolic Stroke or High-Risk Transient Ischemic Attack: Primary Results of the OCEANIC-STROKE Trial. Abstract presented at the American Stroke Association’s International Stroke Conference 2026. New Orleans, LA. February 4-6, 2026.

3. Bayer. A Study to Test Asundexian for Preventing a Stroke Caused by a Clot in Participants After an Acute Ischemic Stroke or After a High-risk Transient Ischemic Attack, a So-called Mini Stroke (OCEANIC-STROKE). ClinicalTrials.gov Identifier: NCT05686070. Updated November 11, 2025. Accessed February 5, 2026. https://clinicaltrials.gov/study/NCT05686070