Key result
Asundexian increases stroke and systemic embolism risk ~279% versus apixaban in AF despite less bleeding.
Why the study?
Asundexian targets the intrinsic coagulation pathway to prevent thrombosis with potentially lower bleeding risk than DOACs and VKAs, warranting synthesis of clinical evidence on its safety, efficacy, and pharmacological properties.
Does asundexian improve safety and efficacy compared to standard anticoagulants in patients at risk for thrombosis?
Systematic Review (n=21,000)
Does asundexian improve safety and efficacy compared to standard anticoagulants in patients at risk for thrombosis?
Effect estimate: HR 3.79 (95% CI 2.46-5.83)
While asundexian reduces bleeding risk compared to apixaban, it demonstrated inferior efficacy in preventing stroke and systemic embolism in patients with atrial fibrillation.
Asundexian should not replace apixaban in atrial fibrillation; challenges further development of this factor XIa inhibitor for stroke prevention.
BACKGROUND: Asundexian, a novel oral Factor XIa (FXIa) inhibitor, targets the intrinsic coagulation pathway to prevent thrombosis while potentially reducing bleeding risk compared to direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs). This systematic review synthesizes clinical evidence on its safety, efficacy, and pharmacological properties in managing arterial and venous thrombotic events. METHODS: Following PRISMA guidelines, we searched PubMed, Embase, Scopus, Cochrane Library, ClinicalTrials.gov, and Web of Science for clinical trials and observational studies on asundexian until January 2025. Inclusion criteria included studies reporting safety, efficacy, and pharmacokinetics/pharmacodynamics (PK/PD) outcomes. Two reviewers independently screened studies and extracted data, with quality assessed using the Cochrane Risk of Bias 2 tool. RESULTS: Eleven trials (n > 21,000, phases 1-3) were included. Asundexian suppressed FXIa activity, with phase 2 trials (e.g., PACIFIC-AF, PACIFIC-STROKE) showing reduced bleeding compared to apixaban. However, the phase 3 OCEANIC-AF trial was terminated early due to inferior efficacy in atrial fibrillation, with higher stroke/systemic embolism rates (2.5%) versus apixaban. PK/PD data support once-daily dosing with minimal drug interactions. Safety concerns include potential abnormal uterine bleeding, with limited data. CONCLUSION: Asundexian shows promise in reducing bleeding but lacks efficacy in high-risk settings like atrial fibrillation. Ongoing trials are needed to define its role in specific thrombotic conditions. CLINICAL TRIAL NUMBER: Not applicable.
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Aldeen et al. (2025) conducted a systematic review in Arterial and venous thrombotic events (n=21,000). Asundexian vs. Placebo, apixaban, or standard anticoagulation was evaluated on Stroke or systemic embolism (OCEANIC-AF trial) (HR 3.79, 95% CI 2.46-5.83). Asundexian demonstrated a favorable bleeding profile but lacked efficacy in atrial fibrillation, leading to early termination of a phase 3 trial due to higher stroke and systemic embolism rates compared to apixaban (HR 3.79).
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