Background
Phase III, double-blind, placebo-controlled RCT (OCEANIC-STROKE). 12,327 patients within 72 hours of noncardioembolic ischemic stroke or high-risk TIA. Inclusion required at least one of: nonlacunar infarct on imaging, history of atherosclerosis, or atherosclerotic plaque on cerebrovascular imaging. Asundexian is a small molecule inhibitor of activated factor XI (FXIa), targeting the intrinsic coagulation pathway. Background antiplatelet therapy (dual or single) continued in both arms.
Interventions and follow up
Arm A: Asundexian 50 mg once daily + antiplatelet therapy
Arm B: Placebo + antiplatelet therapy
Primary endpoint: Ischemic stroke (cause-specific)
mFollow up: Not specified
Arm B: Placebo + antiplatelet therapy
Primary endpoint: Ischemic stroke (cause-specific)
mFollow up: Not specified
Results
Ischemic stroke: 6.2% vs 8.4%, cause-specific HR 0.74, 95% CI 0.65–0.84, P<.001
CV death/MI/stroke (composite): Lower in asundexian arm (specific rates not reported)
Major bleeding: 1.9% vs 1.7%, cause-specific HR 1.10, 95% CI 0.85–1.44 — no significant difference
CV death/MI/stroke (composite): Lower in asundexian arm (specific rates not reported)
Major bleeding: 1.9% vs 1.7%, cause-specific HR 1.10, 95% CI 0.85–1.44 — no significant difference
Adverse events
Main adverse events: Overall adverse events 69.3% vs 70.1%. Serious adverse events 19.2% vs 19.5%. No significant increase in major bleeding with asundexian. Consistent with FXIa inhibitor class profile.
Conclusions
Asundexian added to antiplatelet therapy significantly reduced recurrent ischemic stroke after noncardioembolic stroke or TIA without increasing major bleeding, supporting the concept of FXIa inhibition as a safer antithrombotic approach in ischemic stroke prevention.
Key Limitations
Key Limitations: Noncardioembolic stroke is a heterogeneous population; benefit may vary by stroke mechanism (lacunar vs atherosclerotic vs cryptogenic). No direct comparison with anticoagulation for populations where atrial fibrillation may be a contributor. The magnitude of absolute risk reduction (6.2% vs 8.4%) will need to be translated to NNT across varying baseline risk profiles. Long-term follow-up data are lacking.
Clinical Context
Factor XIa inhibitors represent a novel antithrombotic class with potential safety advantages (dissociation of hemostasis from thrombosis). OCEANIC-STROKE is the first positive phase III trial for FXIa inhibition in stroke prevention. Asundexian (Bayer) joins other FXIa inhibitors in development (abelacimab, milvexian). If approved, this class could shift secondary stroke prevention paradigms, particularly in patients where anticoagulation is contraindicated or undesirable.
References
References: Sharma M et al, NEJM 2026 (OCEANIC-STROKE)