Asundexian Reduces Ischemic Stroke Without Increasing Bleeding Regardless of Infarct Pattern

Asundexian successfully reduced ischemic stroke recurrence without increasing major bleeding, irrespective of the baseline infarct pattern based on magnetic resonance imaging (MRI), according to a substudy of the OCEANIC-STROKE trial.¹

These data were presented at the World Stroke Congress (WSC) 2026 in Seoul, South Korea, by Raed Joundi, MD, assistant professor in the department of medicine at McMaster University, scientist in the Brain Health research program at the Population Health Research Institute (PHRI), and Anne Marie Brune/PHRI Chair in Vascular Dementia at McMaster and PHRI.¹

“OCEANIC-STROKE was a really remarkable finding, with the benefit in stroke reduction not having that increased bleeding typical of antithrombotics,” Joundi told HCPLive in an exclusive interview. “We did this substudy as part of the OCEANIC trial to better phenotype patients with respect to their baseline imaging, infarct pattern, and other markers to see whether any of that information impacts the effect of the treatment.”

OCEANIC-STROKE was a phase 3 double-blind trial evaluating the efficacy of asundexian in addition to antiplatelet therapy in patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA) at risk of recurrent stroke. Patients were eligible for inclusion if they had a nonlacunar infarct on imaging, a history of atherosclerosis, or evidence of atherosclerotic plaque at any location in cerebrovascular imaging. The primary endpoints were time to first ischemic stroke occurrence and first major bleeding occurrence, both recorded ≤31 months.^2,3

A total of 12,327 patients were enrolled in OCEANIC-STROKE, with 6162 randomized to the asundexian arm and 6165 to placebo. Over 19 months of follow-up, ischemic stroke incidence was lower among those receiving asundexian than placebo (6.2% vs 8.4%; cause-specific HR [csHR], 0.74; 95% CI, 0.65-0.84; P <.001). Major bleeding incidence was similar in both groups (1.9% and 1.7%, respectively; csHR, 1.1; 95% CI, 0.85-1.44), establishing that bleeding risk was not increased with treatment, unlike standard antiplatelet therapy.²

In the present study, Joundi and colleagues enrolled consecutive patients with non-cardioembolic stroke, obtaining standardized MRI scans within 5 days of the index event. Infarct patterns were categorized based on number, location, and size of diffusion restricting (DWI+) lesions. The team calculated csHRs to determine whether asundexian’s effects on recurrent ischemic stroke and major bleeding were contingent on baseline infarct pattern.¹

A total of 1126 evaluable MRI scans were included in the study, of which 1076 (95.6%) had DWI+ lesions consistent with acute infarcts. Single small subcortical infarcts, defined as ≤15 mm, occurred in 297 patients, multiple infarcts in 565 patients, ≥1 large infarct, defined as >15 mm, in 512 patients, and ≥1 cortical infarct in 544 patients. The team found that asundexian treatment was associated with a reduction in ischemic stroke (8.2% vs 12.1%; csHR, 0.67; 95% CI, 0.46-0.98), with no statistically significant interaction with infarct pattern. Joundi and colleagues also noted that only 2 intracerebral hemorrhages occurred per group, and no significant increase in major bleeding with asundexian was found.¹

Ultimately, Joundi and colleagues determined that asundexian’s effects had no interaction with infarct patterns. Ischemic stroke was substantially reduced and major bleeding was not increased irrespective of baseline infarct patterns based on MRI scans.¹

“We had a population in this substudy that was at high risk of bleeding, but the risk for intracranial bleeding was very low, not different between the arms,” Joundi said. “I think the safety signal in the main trial is really bolstered by the MRI substudy in this case.”

Editors’ Note: Joundi reports no relevant disclosures.

References

1. Joundi R. Effect of Factor XIa Inhibitor Asundexian on Ischemic Stroke Recurrence According to Baseline Infarct Pattern: MRI Substudy of OCEANIC-STROKE Trial. Presented at the World Stroke Congress (WSC) 2026 in Seoul, South Korea. October 21-23, 2026.

2. Sharma M, Dong Q, Hirano T, et al. Asundexian for Secondary Stroke Prevention. New England Journal of Medicine. 2026;394(15):1467-1479. doi:10.1056/nejmoa2513880

3. Bayer. A Study to Test Asundexian for Preventing a Stroke Caused by a Clot in Participants After an Acute Ischemic Stroke or After a High-risk Transient Ischemic Attack, a So-called Mini Stroke (OCEANIC-STROKE). ClinicalTrials.gov Identifier: NCT05686070. Updated November 12, 2025. Accessed November 3, 2026. https://clinicaltrials.gov/study/NCT05686070