Raed Joundi, MD, is an assistant professor in the department of medicine at McMaster University, a scientist in the Brain Health research program at the Population Health Research Institute (PHRI), and the Anne Marie Brune/PHRI Chair in Vascular Dementia at McMaster and PHRI.

Raed Joundi, MD

Asundexian’s improvements in stroke recurrence irrespective of infarct subtype in patients with 

 have opened up a wide range of potential future research targets for Factor XIa inhibition.

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

 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.

“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 

 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.

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.

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.

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.

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.

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

Videos

Raed Joundi, MD, discusses the implications of his substudy of OCEANIC-STROKE and how it could change secondary prevention in ischemic stroke care.

 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.

Asundexian Reduces Ischemic Stroke Without Increasing Bleeding Regardless of Infarct Pattern

“OCEANIC-STROKE was a really remarkable finding, with the benefit in stroke reduction not having that increased bleeding typical of antithrombotics,” Joundi told 

 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.

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; 

 <.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.

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.

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.

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.

“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.”

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

Raed Joundi, MD, discusses his substudy of the OCEANIC-STROKE trial, demonstrating the safety of Bayer’s investigational FXIa inhibitor across the spectrum of infarct patterns.

Raed Joundi, MD

Articles