Asundexian Cuts Recurrent Stroke Risk Without More Bleeding: Mukul Sharma, MD, MSc

For decades, stroke specialists have faced a frustrating trade-off: The medications that lower the risk of another ischemic stroke almost always raise the risk of bleeding. Antiplatelet drugs and anticoagulants can be highly effective, but their use requires careful patient selection and constant vigilance for hemorrhagic complications. New phase 3 data suggest that targeting factor XIa (FXIa) may finally shift that balance.

Results from the OCEANIC-STROKE trial, presented at the International Stroke Conference 2026, tested the oral FXIa inhibitor asundexian for secondary prevention in people who recently experienced a noncardioembolic ischemic stroke or high-risk transient ischemic attack (TIA).¹ The study enrolled 12,327 participants within 72 hours of their event and randomized them to asundexian 50 mg once daily or placebo, on top of standard antiplatelet therapy. Investigators stratified participants by whether they were planned for single or dual antiplatelet therapy.

Participants had a National Institutes of Health Stroke Scale (NIHSS) score of 15 or lower for stroke or an ABCD2 score of 6 or higher for TIA, along with evidence of atherosclerosis or a nonlacunar infarct. The mean (SD) age was 68 (11) years, and 33% were female. Most qualifying events were ischemic strokes (95%), and 27% of participants had received intravenous thrombolysis and/or mechanical thrombectomy. By TOAST classification, 43% of strokes were attributed to large artery atherosclerosis, 22% to small vessel occlusion, and 30% were of undetermined cause. Dual antiplatelet therapy was planned in 63% of participants at baseline.

The primary efficacy end point was time to first ischemic stroke; the primary safety end point was time to first International Society on Thrombosis and Haemostasis (ISTH) major bleeding event.

According to Mukul Sharma, MD, MSc, professor of neurology at McMaster University in Hamilton, Canada, what stood out most was how consistent the results were. Asundexian reduced the hazard of recurrent ischemic stroke by 26% compared with placebo (HR, 0.74). At the same time, rates of ISTH major bleeding—including intracranial and minor bleeding—were similar between the treatment and placebo groups.

“For the first time, we saw an uncoupling of efficacy and safety,” Sharma said in an interview.

He noted that benefit was seen across age groups, in both men and women, and across stroke subtypes and severities up to an NIHSS score of 15. Importantly, asundexian showed benefit not only in large artery atherosclerosis and small vessel occlusion, but also in stroke of undetermined etiology—a group in which other agents have not clearly outperformed aspirin.

“For the first time in my life, I can say that it seems to work across everything we tested,” Sharma said.

That consistency could make the therapy easier to use in practice. With dual antiplatelet therapy, clinicians are typically cautious, often limiting use to people with minor stroke because of bleeding risk. Sharma suggested that FXIa inhibition may represent a “complete game changer,” allowing clinicians to focus less on balancing bleeding risk against ischemic benefit. “Here it seems to be, we get the benefit without the risk of bleeding,” he said.

Questions remain, including how to manage patients who experience another acute stroke while taking asundexian and whether thrombolytic therapy would be safe in that setting. More data are also needed on use around urgent surgery or trauma.

Still, if the findings hold up in final analyses, asundexian could mark a major shift in secondary stroke prevention—offering broad protection against recurrent ischemic stroke without adding the bleeding burden that has long limited other antithrombotic strategies.

Reference

Sharma M, Joundi RA, Dong Q, et al. Factor XIa inhibition with Asundexian in acute non-cardioembolic stroke or high-risk transient ischemic attack: primary results of the OCEANIC-STROKE trial. Presented at: International Stroke Conference 2026; February 3-6, 2025; New Orleans, LA. Abstract LB009.