Key result
Asundexian reduces ischemic stroke and major cardiovascular events versus placebo without higher major bleeding risk.
Why the study?
Whether the addition of asundexian to antiplatelet therapy is superior to antiplatelet therapy alone for secondary prevention of ischemic stroke is unclear.
Does asundexian added to antiplatelet therapy reduce ischemic stroke in patients with recent noncardioembolic ischemic stroke or high-risk TIA?
RCT (n=12,327)
double-blind
randomly assigned
Does asundexian added to antiplatelet therapy reduce ischemic stroke in patients with recent noncardioembolic ischemic stroke or high-risk TIA?
Hazard Ratio: 0.74 (95% CI 0.65–0.84)
Absolute Event Rate: 6.2% vs 8.4%
p-value: p=<0.001
In patients with recent noncardioembolic ischemic stroke or high-risk TIA, adding asundexian to antiplatelet therapy significantly reduced the risk of recurrent ischemic stroke and major cardiovascular events without increasing the risk of major bleeding.
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Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“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...”
“What makes me believe this is a revolutionary paradigm shift in our ability to prevent stroke is the safety results that came with this improved efficacy, because we saw these benefits without any excess in our primary safety endpoint. But not only that, we actually saw absolutely no significant increase in any of our safety endpoints. This is the first case in history where an anticlotting drug is able to prevent a clotting event without having some offsetting harm from bleeding.”
“For the first time, we saw an uncoupling of efficacy and safety.”
Opens new option for secondary prevention after noncardioembolic stroke; extends factor XI inhibition to arterial cerebrovascular disease.
BACKGROUND: Patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA) are at risk for recurrent stroke. Low factor XI levels are associated with a reduced risk of ischemic stroke. Asundexian inhibits activated factor XI. Whether the addition of asundexian to antiplatelet therapy would be superior to antiplatelet therapy alone for the secondary prevention of ischemic stroke is unclear. METHODS: In this phase 3, double-blind trial, we randomly assigned patients within 72 hours after the onset of a noncardioembolic ischemic stroke or high-risk TIA to receive asundexian (50 mg once daily) or placebo, in addition to planned dual or single antiplatelet therapy. Patients had at least one of the following: a nonlacunar infarct on imaging, a history of atherosclerosis, or evidence of atherosclerotic plaque at any location on cerebrovascular imaging. The primary efficacy outcome was ischemic stroke. The composite of death from cardiovascular causes, myocardial infarction, or stroke was a key secondary outcome. The primary safety outcome was major bleeding. RESULTS: Among 12,327 patients who underwent randomization (6162 to the asundexian group and 6165 to the placebo group), the incidence of ischemic stroke was lower in the asundexian group than in the placebo group (6.2% vs. 8.4%; cause-specific hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.84; P<0.001). The incidence of the composite of death from cardiovascular causes, myocardial infarction, or stroke was lower in the asundexian group than in the placebo group. The incidence of major bleeding was similar in the asundexian group and the placebo group (1.9% and 1.7%, respectively; cause-specific hazard ratio, 1.10; 95% CI, 0.85 to 1.44). The incidence of adverse events was 69.3% in the asundexian group and 70.1% in the placebo group; the incidence of serious adverse events was 19.2% and 19.5%, respectively. CONCLUSIONS: Among patients with noncardioembolic ischemic stroke or high-risk TIA treated with antiplatelet therapy, asundexian at a daily dose of 50 mg resulted in lower risks of ischemic stroke and major cardiovascular events than placebo, without a higher risk of major bleeding. (Funded by Bayer; OCEANIC-STROKE ClinicalTrials.gov number, NCT05686070.).
Sharma et al. (2026) conducted an RCT in noncardioembolic ischemic stroke or high-risk TIA (n=12,327). Asundexian vs. placebo was evaluated on ischemic stroke (HR 0.74, 95% CI 0.65 to 0.84, p=<0.001). Asundexian added to antiplatelet therapy reduced the incidence of ischemic stroke compared to placebo (6.2% vs. 8.4%; HR 0.74; 95% CI, 0.65-0.84; P<0.001).
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