N Engl J Med
Factor XIa inhibitor cuts recurrent stroke risk without the bleeding tradeoff
Clinical Takeaway: In patients with recent noncardioembolic ischemic stroke or high-risk TIA already on antiplatelet therapy, adding the factor XIa inhibitor asundexian reduced recurrent ischemic stroke without a bleeding penalty.
Nearly 1 in 10 patients has another stroke within a year after a noncardioembolic ischemic event despite antiplatelet therapy, but options to intensify prevention have been limited by bleeding risk.
In the phase 3 OCEANIC-STROKE trial, investigators tested whether targeting factor XIa could improve secondary stroke prevention while avoiding the hemorrhagic tradeoffs of conventional anticoagulation. The double-blind trial enrolled 12,327 patients within 72 hours of a noncardioembolic ischemic stroke or high-risk TIA across 37 countries. Patients received asundexian 50 mg once daily or placebo on top of planned single or dual antiplatelet therapy and were followed for a median of about 19 months.
Asundexian significantly lowered the risk of recurrent ischemic stroke, occurring in 6.2% of patients vs. 8.4% with placebo (hazard ratio, 0.74; 95% confidence interval, 0.65–0.84). The absolute risk reduction was approximately 1.9% at one year, translating to a number needed to treat of about 53. The key secondary composite of cardiovascular death, myocardial infarction, or stroke was also reduced.
Importantly, safety outcomes were comparable. Major bleeding occurred in 1.9% of patients receiving asundexian and 1.7% receiving placebo, with no signal for excess intracranial hemorrhage.
“The curves diverged early and continued to separate over time,” said principal investigator Mike Sharma, MD, adding that factor XIa inhibition offers “the ability to uncouple thrombosis from hemostasis.”
An accompanying NEJM editorial called the findings “a promising step,” suggesting factor XI inhibitors may reshape long-term secondary stroke prevention pending longer-term follow-up.
Source: Sharma M, et al; OCEANIC-Stroke Investigators. (2026, April 15). N Engl J Med. Asundexian for Secondary Stroke Prevention