Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity: Prespecified Subgroup Analysis of the ANNEXA-4 Study in Japan

• Published in: Journal of Atherosclerosis and Thrombosis Vol. 31; no. 3; pp. 201 - 213
• Main Authors: Toyoda, Kazunori, Arakawa, Shuji, Ezura, Masayuki, Kobayashi, Rei, Tanaka, Yoshihide, Hasegawa, Shu, Yamashiro, Shigeo, Komatsu, Yoji, Terasawa, Yuka, Masuno, Tomohiko, Kobayashi, Hiroshi, Oikawa, Suzuko, Yasaka, Masahiro
• Format: Journal Article
• Language: English
• Published: Japan Japan Atherosclerosis Society 01.03.2024
• Subjects: Anticoagulation; Antidote; Asian; Bleeding; Intracranial hemorrhage; Original; Intracranial hemorrhage; Anticoagulation; Antidote; Asian; Bleeding
• ISSN: 1340-3478; 1880-3873; 1880-3873
• DOI: 10.5551/jat.64223

Aims: Andexanet alfa, a specific antidote to factor Xa (FXa) inhibitors, has been approved for clinical use in several countries, including Japan, based on the results from the phase 3 trial ANNEXA-4. We aimed to assess the efficacy and safety of andexanet alfa treatment in FXa inhibitor–related acute major bleeding in patients enrolled for ANNEXA-4 in Japan.Methods: This prespecified analysis included patients enrolled at Japanese sites in the prospective, open-label, single-arm ANNEXA-4 trial. Eligible patients had major bleeding within 18 hours of oral FXa inhibitor administration. The coprimary efficacy endpoints were percent change in anti-FXa activity and proportion of patients achieving excellent or good hemostatic efficacy 12 hours post-treatment.Results: A total of 19 patients were enrolled, all of whom had intracranial hemorrhage; 16 patients were evaluable for efficacy. Median percent reduction in anti-FXa activity from baseline to nadir was 95.4% in patients taking apixaban, 96.1% in patients taking rivaroxaban, and 82.2% in patients taking edoxaban. Overall, 14/16 patients (88%) achieved excellent or good hemostasis (apixaban, 5/5; rivaroxaban, 6/7; edoxaban, 3/4). Within 30 days, treatment-related adverse events (AEs) and serious AEs occurred in 2 and 5 patients, respectively. One patient died during follow-up, and 2 patients experienced thrombotic events.Conclusion: Treatment with andexanet alfa rapidly reduced anti-FXa activity with favorable hemostatic efficacy in Japanese patients with acute major bleeding. Serious AEs of thrombotic events during rapid reversal of anti-FXa activity arose as particular safety concerns in this population as with previous studies.