Asundexian lowers recurrent ischemic stroke risk
Adding asundexian to antiplatelet therapy reduced recurrent ischemic stroke without increasing major bleeding.
*Randomized double-blind placebo-controlled trial; Level 1b (OCEBM).

Citation

Sharma M, Dong Q, Hirano T, et al. Asundexian for Secondary Stroke Prevention. N Engl J Med. 2026;394:1467-1479. doi:10.1056/NEJMoa2513880.

Background

Even with antiplatelet medicines, many patients have another ischemic stroke after a recent stroke or transient ischemic attack. This trial tested whether adding asundexian (a clotting-pathway blocker) improves prevention without causing more serious bleeding.

Patients

12,327 adults randomized within 72 hours after noncardioembolic ischemic stroke or high-risk transient ischemic attack, with planned single or dual antiplatelet therapy and evidence/history of artery plaque disease. Excluded: atrial fibrillation or other need for full-dose blood thinners, active clinically important bleeding, or procedure-related/specific-cause stroke.

Intervention

Asundexian 50 mg once daily plus antiplatelet therapy.

Control

Placebo plus antiplatelet therapy.

Outcome

Primary: ischemic stroke. Key secondary: major cardiovascular events (death from cardiovascular causes, heart attack, or stroke). Primary safety: major bleeding.

Follow-up Period

Median 567 days.

Results

Outcome (1-year risk) Asundexian Placebo Absolute risk reduction NNT (1 year) Hazard ratio (95% CI)
Ischemic stroke (primary) 6.2% 8.4% 2.2% 46 0.74 (0.65–0.84)
Any stroke 6.6% 8.8% 2.2% 46 0.74 (0.65–0.84)
Death from cardiovascular causes, heart attack, or stroke 9.2% 11.1% 1.9% 53 0.83 (0.74–0.92)
Death from any cause, heart attack, or stroke 10.5% 12.3% 1.8% 56 0.85 (0.77–0.95)
Disabling or fatal stroke 2.1% 3.0% 0.9% 112 0.69 (0.55–0.87)

Major bleeding was similar: 1.9% with asundexian vs 1.7% with placebo (not significant).

Efficacy analyses included all randomized patients (intention-to-treat). Because the 90-day ischemic stroke result was not statistically significant, later outcomes were not formally tested in the prespecified sequence.

Limitations

Few patients had more severe strokes, and few entered after transient ischemic attack. About 26% stopped study drug. Black patients were underrepresented, limiting certainty for that group.

Funding

Bayer; sponsor maintained the database.

Clinical Application

For recent noncardioembolic stroke or high-risk transient ischemic attack on antiplatelets, consider adding asundexian 50 mg daily to reduce recurrent ischemic stroke risk.