Bleeding With Asundexian Versus Placebo in Patients With Noncardioembolic Ischemic Stroke or High-Risk TIA: OCEANIC-STROKE Randomized Trial

BACKGROUND: OCEANIC-STROKE (XXX) showed that asundexian added to antiplatelet therapy reduced ischemic stroke without significantly increasing bleeding in patients with noncardioembolic ischemic stroke or high-risk transient ischemic attack. We characterized bleeding categories, sites, and key subgroups. METHODS: In the safety population, 12 254 participants received at least 1 dose of asundexian (n=6124) or placebo (n=6130). Bleeding was categorized by International Society on Thrombosis and Haemostasis criteria as major, clinically relevant nonmajor (CRNM), or minor. While-on-treatment analyses included events through 2 days after the last dose, with death and permanent discontinuation as competing risks. RESULTS: Major bleeding occurred in 117 (1.9%) participants with asundexian and 107 (1.7%) with placebo (cause-specific hazard ratio [csHR], 1.10 [95% CI, 0.85-1.44]; P=0.46). Major or CRNM bleeding occurred in 339 (5.5%) and 307 (5.0%), respectively (csHR, 1.12 [95% CI, 0.96-1.30]; P=0.16), and any bleeding in 763 (12.5%) and 752 (12.3%) (csHR, 1.02 [95% CI, 0.93-1.13]; P=0.65). Treatment effects for major and major or CRNM bleeding were consistent across prespecified subgroups, including planned dual antiplatelet therapy. Symptomatic intracranial hemorrhage occurred in 41 (0.7%) and 36 (0.6%) participants. Any gastrointestinal bleeding occurred in 186 (3.0%) and 147 (2.4%) (csHR, 1.28 [95% CI, 1.03-1.59]), and lower gastrointestinal bleeding in 102 (1.7%) and 59 (1.0%) (csHR, 1.75 [95% CI, 1.27-2.41]), primarily rectal bleeding. Any procedure-related bleeding and any mucosal bleeding did not differ significantly. CONCLUSIONS: Asundexian added to antiplatelet therapy reduced ischemic stroke without significantly increasing major, major or CRNM, or any bleeding. Lower gastrointestinal bleeding was more frequent with asundexian, whereas treatment effects on major and major or CRNM bleeding were consistent across prespecified subgroups. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05686070.