Asundexian in Secondary Stroke Prevention After Noncardioembolic Events

Key Takeaways

• Asundexian was associated with a lower risk of ischemic stroke versus placebo in patients with recent noncardioembolic ischemic stroke or high-risk transient ischemic attack.
• The randomized phase 3 comparison evaluated efficacy outcomes alongside bleeding risk in a secondary prevention setting.
• Major bleeding rates were similar between groups despite improved efficacy outcomes.

The trial was conducted in the secondary prevention setting after ischemic cerebrovascular events. Patients were randomized within 72 hours of a qualifying noncardioembolic ischemic stroke or high-risk transient ischemic attack. Asundexian, a factor XIa inhibitor, was administered at 50 mg once daily in addition to planned single or dual antiplatelet therapy, and was studied against placebo in a randomized design centered on prevention of recurrent vascular events.

The primary efficacy outcome was ischemic stroke. The incidence of ischemic stroke was 6.2% with asundexian and 8.4% with placebo, corresponding to a cause-specific hazard ratio of 0.74 (95% CI, 0.65 to 0.84; P<.001). A key secondary composite outcome of cardiovascular death, myocardial infarction, or stroke was also lower in the asundexian group.

Bleeding-related outcomes were the main safety focus. Major bleeding occurred in 1.9% of patients receiving asundexian and 1.7% receiving placebo, with a hazard ratio of 1.10 (95% CI, 0.85 to 1.44). Overall adverse events (69.3% vs 70.1%) and serious adverse events (19.2% vs 19.5%) were similar between groups.

Within the trial context, asundexian reduced ischemic stroke and major cardiovascular events compared with placebo without an increased risk of major bleeding, in a population of 12,327 patients treated after recent ischemic cerebrovascular events.