Key result
Factor XIa inhibitors reduce recurrent ischemic stroke ~23% vs. placebo without increasing major bleeding.
Why the study?
Recurrent stroke risk remains high after noncardioembolic ischemic stroke despite guideline-recommended antiplatelet therapy. Factor XIa inhibitors offer a novel antithrombotic strategy that targets pathological thrombosis while preserving hemostasis, motivating an evaluation of their efficacy and safety for secondary stroke prevention.
Do Factor XIa inhibitors reduce the incidence of recurrent ischemic stroke in patients with noncardioembolic ischemic stroke or high-risk transient ischemic attack?
Meta-Analysis (n=16,501)
Do Factor XIa inhibitors reduce the incidence of recurrent ischemic stroke in patients with noncardioembolic ischemic stroke or high-risk transient ischemic attack?
Factor XIa inhibitors significantly reduce recurrent ischemic stroke by 23% in patients with noncardioembolic ischemic stroke or high-risk TIA without increasing major bleeding or intracranial hemorrhage.
Answers are grounded in this paper and cite their sources.
Supports Factor XIa inhibitors for secondary prevention after noncardioembolic stroke; confirms efficacy and safety in pooled RCT data.
Background Despite guideline-recommended antiplatelet therapy, recurrent stroke risk remains high following noncardioembolic ischemic stroke (NCIS). Factor XIa inhibitors, including asundexian and milvexian, selectively target pathological thrombosis while preserving hemostasis, representing a novel antithrombotic strategy. This meta-analysis aims to assess the efficacy and safety of Factor XIa inhibitors for secondary prevention of NCIS. Methods Following PRISMA guidelines, a systematic search was conducted in PubMed, Cochrane, Scopus, and EMBASE databases up to May 8, 2026. Randomized controlled trials (RCTs) were included, comparing Factor XIa inhibitors with placebo in patients with NCIS or high-risk transient ischemic attack. The primary outcome was the incidence of recurrent ischemic stroke, and secondary efficacy and safety outcomes included all-cause mortality, major bleeding, clinically relevant non-major bleeding (CRNM), and intracranial hemorrhage (ICH). Data were extracted and analyzed using random-effects models to calculate risk ratios (RR) and 95% confidence intervals (CI). Results Three RCTS (N=16501) were included. The pooled analysis showed that Factor XIa inhibitors significantly reduced the risk of recurrent ischemic stroke than placebo (RR 0.77, 95% CI 0.68-0.86, P < 0.00001; I 2 = 0%). The use of Factor XIa inhibitors did not significantly reduce all-cause mortality (RR 1.00, 95% CI 0.85-1.18, P = 0.98, I 2 = 0%). For safety outcomes, there was no significant difference between the two groups for major bleeding (RR 1.13, 95% CI 0.89-1.45, P = 0.32; I 2 = 0%), CRNM (RR 1.54, 95% CI 0.89-2.66, P = 0.12, I 2 = 62%), and ICH (RR 1.11, 95% CI 0.73-1.70, P = 0.62; I 2 = 0%). Conclusion In conclusion, Factor XIa inhibitors significantly reduce the risk of recurrent ischemic stroke in patients with NCIS. No increased risk of major bleeding, CRNM, and ICH was seen with Factor XIa inhibitors compared with placebo. These findings suggest that Factor XIa inhibitors are a promising class of drugs for secondary stroke prevention in patients with NCIS and also have a stable hemostatic profile.
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Ejaz et al. (2026) conducted a meta-analysis in Noncardioembolic ischemic stroke or high-risk transient ischemic attack (n=16,501). Factor XIa inhibitors (including asundexian and milvexian) vs. Placebo (with background guideline-recommended antiplatelet therapy) was evaluated on Incidence of recurrent ischemic stroke (RR 0.77, 95% CI 0.68-0.86, p=<0.00001). Factor XIa inhibitors reduced the risk of recurrent ischemic stroke compared with placebo without increasing major bleeding.
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