Asundexian for Secondary Stroke Prevention: Factor XIa Inhibition and the OCEANIC-STROKE Trial

Patients surviving a non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA) face a substantially elevated risk of recurrent stroke despite current antiplatelet-based secondary prevention. Asundexian is an investigational oral small-molecule inhibitor of activated factor XIa (FXIa) that targets the contact activation pathway of coagulation, offering potential thrombus prevention without impairment of primary hemostasis. The OCEANIC-STROKE trial was a phase 3, international, multicenter, randomized, double-blind, placebo-controlled, event-driven study. A total of 12,327 patients were enrolled within 72 hours of a qualifying event across 37 countries and randomized to asundexian 50 mg once daily or placebo, on top of planned single or dual antiplatelet therapy. The primary efficacy endpoint was time to ischemic stroke; the primary safety endpoint was ISTH-defined major bleeding. Asundexian significantly reduced the incidence of ischemic stroke compared with placebo (6.2% vs. 8.4%; cause-specific hazard ratio [csHR], 0.74; 95% CI, 0.65–0.84; P<0.001), representing a 26% relative risk reduction. Major bleeding was similar in both groups (1.9% vs. 1.7%; csHR, 1.10; 95% CI, 0.85–1.44). Consistent benefit was demonstrated across all prespecified subgroups, including stroke subtype, index event, use of reperfusion therapy, age, sex, and antiplatelet strategy. OCEANIC-STROKE is the first successful phase 3 trial of a factor XIa inhibitor for secondary stroke prevention, demonstrating that asundexian reduces recurrent ischemic stroke without increasing major bleeding, potentially establishing a new therapeutic paradigm for this high-risk population.