Stroke Subtype Does Not Affect Efficacy of Asundexian for Second Stroke Prevention

The factor XIa (FXIa) inhibitor asundexian significantly reduced recurrent ischemic stroke across major noncardioembolic stroke subtypes without increasing major bleeding risk in a prespecified secondary analysis of the OCEANIC-STROKE trial (NCT05686070), supporting its potential as a broadly effective recurrent stroke prevention strategy.1 These results were presented as a late-breaking abstract in the wake of impressive late-breaking main trial findings at the 2026 International Stroke Conference held in New Orleans, Louisiana.

“You've already seen the impressive primary results of the OCEANIC-STROKE study, which were presented this morning by my colleague, Mike Sharma, [MD, MSc, FRCPC], where treatment with asundexian led to a 26% reduction in the hazard of the primary efficacy end point of time to first occurrence of ischemic stroke without any excess in major bleeding,”2 said lead author and presenter Ashkan Shoamanesh, MD, FRCPC, FESO, associate professor of medicine (neurology) at McMaster University in Hamilton, Canada, who holds the Marta and Owen Boris Chair in Stroke Research and Care. He emphasized the importance of the finding that there was no significant increase for any of the prespecified end points.

The OCEANIC-STROKE subgroup analysis findings, in tandem with the main results presented at ISC 2026, suggest that targeting factor XIa could be a safe way to intensify antithrombotic therapy following noncardioembolic stroke, regardless of underlying etiology. | Image credit: jolygon - stock.adobe.com

The overall OCEANIC-STROKE results made waves at ISC 2026, and the prespecified secondary analysis focused on qualifying ischemic stroke subtypes.1

“As we know, a noncardioembolic ischemic stroke is an umbrella term that has heterogeneous ischemic stroke etiologies within it,” Shoamanesh said. “And in our earlier phase 2 PACIFIC-STROKE study [NCT04304508], there was some suggestion of heterogeneity in the treatment effect according to presenting etiology, with a greater treatment effect in patients with large artery atherosclerosis.”3

The global, phase 3, randomized, double-blind OCEANIC-STROKE trial enrolled 12,327 patients with recent acute noncardioembolic ischemic stroke (NIHSS ≤ 15) or high-risk transient ischemic attack (TIA; ABCD2 ≥ 6) across 702 sites in 37 countries. Of these, 11,676 participants (95%) had a qualifying ischemic stroke and were included in the subtype analysis.

Patients were randomized within 72 hours of symptom onset to receive asundexian (50 mg once daily) or placebo, on top of standard antiplatelet therapy, and followed for up to 31 months. Stroke subtypes were classified by investigators using TOAST criteria, and 3 main groups emerged: 43% (n = 5028) of strokes were due to large artery atherosclerosis, 22% (n = 2591) were due to small vessel occlusive disease, and 30% (n = 3504) were classified as stroke of undetermined etiology. Shaomanesh noted that in the stroke of undetermined etiology cohort, they conducted a sensitivity analysis looking at patients who met the criteria for embolic stroke of undetermined source (ESUS).

“A trial of this nature and this scale provides really large subgroups that are informative in determining heterogeneity and treatment effect, and whether what we saw in the overall population generalizes to the stroke patients that we see in practice,” Shaomanesh said.

Earlier in the day, it was reported that asundexian reduced the primary end point of time to first ischemic stroke by 26% compared with placebo, with no excess in major bleeding or intracranial hemorrhage.2 The new secondary analysis demonstrated that these benefits were consistent across stroke mechanisms.1

“We saw clear reductions in ischemic stroke irrespective of qualifying subtype,” Shoamanesh said, noting cause-specific hazard ratios ranging from 0.61 to 0.82 across groups, with no significant interaction—suggesting a uniform treatment effect. There were also reductions in all stroke, disabling stroke, and fatal stroke risks across the qualifying ischemic subtypes.

In the 3 main subgroups, there was early separation in cause-specific cumulative incidence curves and continued separation throughout follow-up in favor of asundexian, in line with the overall results presented by Sharma.1,2

Importantly, safety outcomes remained favorable across subtypes.1 There was no increase in the main safety end point of major bleeding by International Society on Thrombosis and Haemostasis criteria, symptomatic intracranial hemorrhage, or hemorrhagic stroke in any subgroup.

“It's also worth noting that hemorrhagic strokes were numerically less with asundexian vs placebo across each subgroup, including those with small vessel occlusive disease, who are at greatest risk for this end point,” Shoamanesh said.

In the ESUS subgroup, a traditionally challenging group to treat, asundexian was associated with a 47% reduction in recurrent ischemic stroke compared with placebo, although this finding was not statistically significant, Shoamanesh noted. However, there was no excess in risk of harm.

These findings, in tandem with the main results presented at ISC 2026, suggest that targeting factor XIa may offer a safe way to intensify antithrombotic therapy in patients with noncardioembolic stroke, regardless of underlying etiology.

“Impressively, these findings were consistent in patients with qualifying ESUS, expanding this new paradigm to this subgroup of patients with qualifying ischemic strokes of undetermined ideology,” Shoamanesh said. “And now, asundexian, on the basis of these results, provides a novel, efficacious, safe, second stroke prevention treatment for patients with noncardioembolic ischemic stroke, irrespective of underlying etiology.”

References

1. Shoamanesh A, Joundi RA, Dong Q, et al. Qualifying ischemic stroke subtypes and response to asundexian: prespecified secondary analysis of the OCEANIC-STROKE trial. Presented at: International Stroke Conference 2026; February 4-6, 2026; New Orleans, LA. Abstract LB020.

2. Sharma M, Joundi R, Eikelboom, et al. Factor XIa inhibition with asundexian in acute non-cardioembolic stroke or high-risk transient ischemic attack: primary results of the OCEANIC-STROKE trial. Presented at: International Stroke Conference 2026; February 4-6, 2026; New Orleans, LA. Abstract LB009.

3. Shoamanesh A, Mundl H, Smith EE, et al. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet. 2022;400(10357):997-1007. doi:10.1016/S0140-6736(22)01588-4