Asundexian lowered the risk of ischemic stroke and major cardiovascular events, without increasing the risk of major bleeding, in patients with noncardioembolic stroke or high-risk transient ischemic attack (TIA) taking antiplatelet therapy, according to results from the phase 3, double-blind OCEANIC-STROKE trial, published April 15 in NEJM.

Mukul Sharma, MD, et al., randomized 12,327 patients within 72 hours after the onset of noncardioembolic ischemic stroke or high-risk TIA to either asundexian 50 mg daily or placebo as an addition to planned dual or single antiplatelet therapy. The primary efficacy endpoint was ischemic stroke, and the primary safety endpoint was major bleeding. The median follow up was 567 days.

The incidence of the primary efficacy endpoint was lower in the treatment group than placebo group (6.2% vs. 8.4%; cause-specific hazard ratio, 0.74; 95% CI, 0.65-0.84; p<0.001), while similar rates of the primary safety endpoint were observed in both groups (1.9% and 1.7%, respectively; cause-specific hazard ratio, 1.10; 95% CI, 0.85-1.44).

A key secondary endpoint, the composite of death from cardiovascular causes, myocardial infarction or stroke, occurred less in the treatment group. Adverse events were seen in 69.3% of patients in the treatment group and 70.1% in the placebo group; serious adverse event rates were 19.2% and 19.5%, respectively.

"Previous attempts at combination antithrombotic therapy for long-term secondary stroke prevention have been unsuccessful because of a lack of efficacy, an increased risk of bleeding, or both," write the authors. "Our results showed that the addition of asundexian is an effective and safe therapeutic option for patients treated with antiplatelet therapy for secondary stroke prevention."

In an accompanying editorial comment, Marion Boulanger, MD, PhD, adds: "Asundexian appears to be a very promising option for secondary prevention after noncardioembolic ischemic stroke or TIA. However, further studies of factor XI inhibitors with longer follow-up (e.g., 5 or 10 years) are necessary to determine whether the net clinical benefit will be maintained over time."