How Asundexian’s Approval Could Reshape Antithrombotic Therapy in Noncardioembolic Stroke: Mike Sharma, MD, MSc

Patients who survive an ischemic stroke remain at substantial risk of a second event. In a systematic review and meta-analysis of population-based studies, recurrence rates ranged from 5.7% to 51.3%, and the researchers noted that recurrence appears largely unchanged over time despite the use of secondary prevention.¹ Oral anticoagulation is the mainstay for cardioembolic stroke related to atrial fibrillation. For patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA), however, the American Heart Association/American Stroke Association recommends antiplatelet therapy rather than oral anticoagulation to reduce the risk of recurrence.²

Recently, the FDA approved asundexian (Sunharbo; Bayer) 50-mg tablets. It is the first factor XIa inhibitor, indicated in combination with antiplatelet therapy to reduce the risk of stroke in adults with a recent mild-to-moderate noncardioembolic ischemic stroke (NIH Stroke Scale [NIHSS] ≤ 15) or high-risk TIA.³ The approval was based on the phase 3 OCEANIC-STROKE trial (NCT05686070), which randomly assigned 12,327 patients within 72 hours of symptom onset to asundexian or placebo on top of antiplatelet therapy.

Overall, ischemic stroke occurred in 6.2% of the asundexian group vs 8.4% of the placebo group (HR, 0.74; 95% CI, 0.65-0.84), and major bleeding occurred in 1.9% vs 1.7%, respectively.⁴ According to the prescribing information, major bleeding rates were higher with asundexian during the first 90 days of treatment and among patients older than 75 years.⁵

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“Our ultimate goal is to get the risk of recurrent stroke as close to zero as we can, and this is a major advance in that.”

To discuss the approval and its clinical implications, NeurologyLive® spoke with Mike Sharma, MD, MSc, professor of medicine and neurology at McMaster University, senior scientist at the Population Health Research Institute, and principal investigator of the OCEANIC-STROKE trial. Sharma highlighted how direct oral anticoagulants (DOACs) have advanced cardioembolic stroke prevention, while treatment options for noncardioembolic stroke have lagged behind. He described the approval as an important step toward expanding antithrombotic treatment options for patients.

Sharma outlined several key findings from OCEANIC-STROKE, including reductions in ischemic stroke with asundexian on top of antiplatelet therapy, no significant increase in major bleeding or intracerebral hemorrhage, and consistent benefits across stroke subtypes and severity. He also discussed a signal for increased lower gastrointestinal bleeding and findings from an MRI substudy of approximately 1100 patients, which showed no excess bleeding despite cerebral microbleeds being present in roughly 40% of participants. He noted, however, that patients with prior spontaneous intracerebral hemorrhage were excluded from the trial.

REFERENCES
1. Kolmos M, Christoffersen L, Kruuse C. Recurrent ischemic stroke – a systematic review and meta-analysis. J Stroke Cerebrovasc Dis. 2021;30(8):105935. doi:10.1016/j.jstrokecerebrovasdis.2021.105935
2. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52(7):e364-e467. doi:10.1161/STR.0000000000000375
3. FDA approves first factor XIa inhibitor to help prevent stroke in certain adults at high risk. News release. US Food and Drug Administration. November 9, 2026. Accessed November 10, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-factor-xla-inhibitor-help-prevent-stroke-certain-adults-high-risk
4. Sharma M, Dong Q, Hirano T, et al. Asundexian for secondary stroke prevention. N Engl J Med. 2026;394(15):1467-1479. doi:10.1056/NEJMoa2513880
5. Bayer’s SUNHARBO (asundexian), 50 mg tablets, the first and only factor XIa inhibitor, approved by the U.S. FDA to reduce the risk of stroke in adults with recent non-cardioembolic ischemic stroke or high-risk transient ischemic attack, in combination with antiplatelet therapy. News release. Bayer. November 9, 2026. Accessed November 10, 2026. https://www.bayer.com/en-us/united-states/news-and-stories/2026/asundexian-fda