1. Asundexian 50 mg resulted in a lower rate of bleeding compared to apixaban 5 mg twice daily.
2. The rate of adverse events in all three treatment groups was comparable.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Direct oral anticoagulants (DOACs) are recommended as first-line therapy in patients with atrial fibrillation with risk factors for thromboembolic events, such as a stroke. However, a major concern with DOACs is the risk of bleeding. Asundexian is an oral factor XIa inhibitor that may decrease the risk of bleeding without affecting hemostasis, compared with DOAC therapy. This randomized double-blind trial aimed to compare the safety and efficacy of asundexian with that of apixaban in patients with atrial fibrillation. Patients were assigned to one of three treatment groups: asundexian 20 mg once daily, asundexian 50 mg once daily, or apixaban 5 mg twice daily. The primary outcome was the risk of major or non-major bleeding as per the International Society on Thrombosis and Hemostasis (ISTH) criteria, while key secondary outcomes included all types of bleeding. According to study results, patients assigned to asundexian 20 mg and 50 mg reported lower risk of bleeding compared to apixaban 5 mg twice daily. The incidence of adverse events was similar between all groups. This study was strengthened by a double-blind design with patients from various countries which increases the generalizability of findings.
In-depth [randomized-controlled trial]: Between Jan 30, 2020, and Jun 21, 2021, 862 patients were enrolled across 93 sites in Europe, Canada, and Japan. Included were those aged ≥ 45 years with atrial fibrillation, a CHA2DS2-VASc ≥ 2 if male or ≥ 3 if female, and high bleeding risk. Altogether, 753 patients (249 to asundexian 20 mg, 254 to asundexian 50 mg, and 250 to apixaban 5 mg twice daily) were included in the analysis. Mean patient age was 73.7 years (standard deviation [SD] 8.3) with an average CHA2DS2-VASc score of 3.9 (SD 1.3). The primary outcome of bleeding was lower in the asundexian group (asundexian 20 mg: incidence proportion [IP] 0.50, 95% confidence interval [CI] 0.14-1.68; asundexian 50 mg: IP 0.16, 95% CI 0.01-0.99) compared to apixaban (pooled asundexian: IP 0.33, 90% CI 0.09-0.97). At peak concentrations, asundexian 50 mg resulted in greater inhibition of Factor XIa activity than asundexian 20 mg (94% vs. 90%). Furthermore, all three intervention groups had comparable adverse events (47% with asundexian 20 mg and 50 mg, and 49% with apixaban 5 mg twice daily). Overall, findings from this study suggest that asundexian decreases the rate of bleeding compared to apixaban in patients with atrial fibrillation.
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