Asundexian and the Role of Factor XIa Inhibition in Secondary Stroke Prevention

Asundexian’s improvements in stroke recurrence irrespective of infarct subtype in patients with ischemic stroke have opened up a wide range of potential future research targets for Factor XIa inhibition.

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

“There were suspicions that those with a small vessel occlusion may not respond as well to asundexian, and that’s because there are different mechanisms hypothesized for small vessel occlusion; not only thrombosis, but also microatheroma, endothelial dysfunction, and inflammation,” Joundi told HCPLive in an exclusive interview. “I think that means thrombosis is necessarily part of the pathway of small vein occlusions. Now, whether it’s a terminal part of the pathway after other changes have taken place, that’s something we can’t really answer.”

Joundi’s analysis collected standardized MRI scans from a portion of the patients included in the OCEANIC-STROKE trial. Briefly, OCEANIC-STROKE was a phase 3, double-blind trial enrolling patients with nonlacunar infarcts on imaging, evidence of atherosclerotic plaque at any location in cerebrovascular imaging, or a history of atherosclerosis. These patients were treated with either asundexian or placebo on top of antiplatelet therapy.^1,2

A total of 12,327 patients were enrolled in OCEANIC-STROKE – of these, 6162 received asundexian and 6165 received placebo. Ischemic stroke incidence was substantially lower in the treatment arm, while major bleeding incidence was similar across both groups. This indicated asundexian’s comparative efficacy, as well as its minimal impact on bleeding. These data also positioned FXIa inhibition as a promising new approach to stroke prevention.²

Joundi and colleagues collected a total of 1126 evaluable MRI scans, identifying 1076 scans with diffusion restricting (DWI+) lesions consistent with acute infarcts. 297 scans showed single small subcortical infarcts, while 565 showed multiple infarcts, 512 showed ≥1 large infarct, and 544 showed ≥1 cortical infarct. Over 19 months of follow-up, the team noted substantial reductions in ischemic stroke in the asundexian arm (8.2% vs 12.1%; cause-specific HR, 0.67; 95% CI, 0.46-0.98), with no significant interaction with infarct pattern.¹

In regard to secondary stroke prevention, Joundi noted that these data reflect significantly less need to separate out infarct patterns when using FXIa inhibition in patients at risk of recurrent stroke. Joundi believes that asundexian’s consistent benefit across a range of infarct patterns in the substudy can be expanded to small versus large vessel infarcts.

However, Joundi also notes that clinicians still need to be vigilant in preventing secondary stroke through other methods, including vascular risk reduction, hypertension and cholesterol management, and so on. Additionally, although the study displayed a long-term benefit with asundexian, Joundi discusses a need for further investigation at a longer time point to collect MRI scans and confirm the lasting benefit.

“Because asundexian was shown to have a long-term effect in the main trial, with the curves diverging over time, it would be very interesting to design a future trial that actually has MRIs done at much later time points, to see if this long-term reduction in recurrent stroke actually improves markers on the MRI,” Joundi said. “These are some future areas of interest for consideration.”

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