Asundexian Reduces Stroke Incidence Without Increasing Bleeding, With Ashkan Shoamanesh, MD

Asundexian, an investigational Factor XIa inhibitor, lowers the risk of stroke in patients who recently experienced non-cardioembolic stroke or a transient ischemic attack (TIA) without increasing bleeding, according to data from OCEANIC-STROKE.1

Despite secondary prevention strategies, 5.1% of patients with ischemic stroke or TIA have a recurrent stroke within 1 year – after 5 years, 22% of patients who had survived the event are disabled or dead. Dual antiplatelet therapy incompletely reduces this risk, and long-term use is associated with higher risks of major hemorrhage. FXIa inhibition approaches the condition from a new angle, potentially circumventing these issues.1,2

“Not only are we not seeing excess in major bleeding, but we also didn’t see excess in minor bleeding,” Ashkan Shoamanesh, MD, associate professor of medicine and Marta and Owen Boris Chair in Stroke Research and Care at McMaster University, told HCPLive in an exclusive interview. “Although minor bleeding is a less immediate clinical consequence regarding health, it certainly still is very significant, because it results in substantial psychological distress for patients and leads to non-compliance, which leads to less efficacy. It’s frankly historic to have a trial of this size and to have confidence in the results, and to see no excess risk with an antithrombotic versus placebo.”

OCEANIC-STROKE was a phase 3, double-blind, event-driven, randomized, placebo-controlled trial conducted at 702 centers across 37 countries. Patients were eligible if they were ≥18 years old with a non-cardioembolic ischemic stroke or high-risk TIA within 72 hours after the onset of symptoms and had a plan for treatment with dual or single antiplatelet therapy. Those with a history of atrial fibrillation or other conditions with an indication for anticoagulation, active nontrivial bleeding, or a qualifying stroke related to a procedure or other specific cause were excluded.2

After enrollment, patients were randomly assigned in a 1:1 ratio to either asundexian 50 mg daily or matching placebo, on top of planned dual or single antiplatelet therapy. The trial’s primary outcome was the first occurrence of ischemic stroke, which was determined to have occurred if there was a new focal neurologic deficit or clinically meaningful worsening of an existing deficit persisting for ≥24 hours. The primary safety outcome was major bleeding, including fatal bleeding, symptomatic bleeding in a critical area or organ, and clinically overt bleeding resulting in a hemoglobin reduction of ≥2 g/dL.2

A total of 12,327 patients were randomized, with 6162 assigned to the asundexian group and 6165 to placebo. A total of 45 patients withdrew consent, and 39 were lost to follow-up. The mean age of the final group of patients was 68 years. 11,677 patients presented with ischemic stroke, while the remainder had TIA. Median follow-up was 567 days (interquartile range [IQR], 377-729).2

Ultimately, Shoamanesh and colleagues found that ischemic stroke incidence was substantially lower in the asundexian group than the placebo group (6.2% vs 8.4%; cause-specific HR, 0.74; 95% CI, 0.65-0.84; P <.001). The incidence of a composite of death from cardiovascular causes, myocardial infarction, or stroke was also lower in the asundexian arm. Major bleeding incidence was similar between both arms (1.9% and 1.7%, respectively; cause-specific HR, 1.1; 95% CI, 0.85-1.44). Adverse events occurred in 69.3% of the asundexian group and 70.1% in the placebo group – serious adverse events had an incidence of 19.2% and 19.5%, respectively.2

The team concluded that treatment with asundexian substantially reduced the risk of ischemic stroke and major cardiovascular events compared with placebo, without increasing the risk of major bleeding in patients. Shoamanesh and colleagues believe that these data mark the beginning of a major shift in ischemic stroke treatment, and in cardiovascular disease overall, as a result of FXIa inhibition’s success.2

“I think this is just the beginning of a large paradigm shift in our treatment of patients with cardiovascular disease,” Shoamanesh said. “Certainly, to date, there have been challenges with factor XI and other disease states. But I suspect the reason for that is that we just haven’t found the right recipe yet – either with higher doses of existing agents or with combination treatments, factor XI is going to be used more widely across the spectrum of cardiovascular disease and venous thromboembolic disease.”

Editors’ Note: Shoamanesh reports disclosures with the Heart and Stroke Foundation of Canada, the Marta and Owen Boris Foundation, Bayer AG, Daiichi Sankyo, AstraZeneca, Octapharma, Inc., and others.

References

1. McMaster University. New anti-clotting medication lowers risk of stroke without added bleeding. Eurekalert. April 15, 2026. Accessed April 20, 2026. https://www.eurekalert.org/news-releases/1123838

2. Sharma M, Dong Q, Hirano T, et al. Asundexian for secondary stroke prevention. NEJM.. 2026;394(15):1467-1479. doi:10.1056/nejmoa2513880