Asundexian reduces recurrent ischemic stroke without increasing bleeding risk

In OCEANIC-STROKE, the FXIa inhibitor asundexian reduced the risk of ischemic stroke in patients with noncardioembolic ischemic stroke or high-risk TIA compared with placebo, without increasing the risk of major bleeding.

This summary is based on the publication of Sharma M, Dong Q, Hirano T, et al. - Asundexian for Secondary Stroke Prevention. N Engl J Med. 2026 Apr 16;394(15):1467-1479. doi: 10.1056/NEJMoa2513880.

Introduction and methods

Background

Patients with an ischemic stroke or transient ischemic attack (TIA) are at risk of recurrent stroke despite antiplatelet therapy [1-3]. Low factor XI levels are associated with a reduced risk of intracerebral bleeding, whereas increased factor XI levels are associated with higher risk of ischemic stroke [4-5]. Asundexian is an inhibitor of activated factor XI [6]. In a phase 2 trial, asundexian added to antiplatelet therapy reduced the occurrence of symptomatic ischemic stroke in patients with noncardioembolic ischemic stroke, without increasing major or clinically relevant non-major bleeding [7].

Aim of the study

The aim of the study was to evaluate the efficacy and safety of asundexian for secondary stroke prevention in patients with ischemic stroke or high-risk TIA.

Methods

The OCEANIC-STROKE (Oral Factor Eleven A Inhibitor Asundexian as Novel Anti thrombotic Stroke) trial was a phase 3, double-blind, event driven, randomized, placebo-controlled trial, in which 12,327 patients within 72 hours after a noncardioembolic ischemic stroke (n=11.677 patients) or high-risk TIA (n=650 patients) were randomized to asundexian 50 mg once daily or placebo, on top of planned single or dual antiplatelet therapy. Median follow-up was 567 days (IQR: 377-729).

Outcomes

The primary efficacy outcome was the first occurrence of ischemic stroke. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Haemostasis (ISTH).

Main results

• The primary efficacy outcome occurred in 384 of 6162 patients (6.2%) in the asundexian group and in 518 of 6165 patients (8.4%) in the placebo group (cause-specific (cs) HR; 0.74; 95%CI: 0.65-0.84; P<0.001).
• The incidence of ischemic or hemorrhagic stroke was lower in the asundexian group compared with the placebo group (6.6% vs. 8.8%; csHR: 0.74; 95%CI: 0.65-0.84; P<0.001), as was the incidence of death from cardiovascular causes, MI, or stroke (9.2% vs. 11.1%; csHR: 0.83; 95%CI: 0.74-0.92; P<0.001).
• ISHT major bleeding occurred in 1.9% of patients in the asundexian group and in 1.7% of the patients in the placebo group (csHR: 1.10; 95%CI: 0.85-1.44; P=0.46).
• Major or clinically relevant nonmajor bleeding occurred in 5.5% of patients in the asundexian group and in 5.0% of patients in the placebo group (csHR: 1.12; 95%CI: 0.96-1.30; P=0.16).
• The incidence of serious adverse events was similar between the asundexian and placebo group (69.3% vs. 70.1%), as was the incidence of serious adverse events (19.2% vs. 19.5%).

Conclusion

In OCEANIC-STROKE among patients with noncardioembolic ischemic stroke or high-risk TIA, adding asundexian to antiplatelet therapy reduced the risk of ischemic stroke compared with placebo, without increasing the risk of major bleeding.

Find this article online at N Engl J Med.

References

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