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
Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.
Department of Neurology, Steel Memorial Yawata Hospital.
J Atheroscler Thromb. 2024 Mar 1;31(3):201-213. doi: 10.5551/jat.64223. Epub 2023 Aug 26.
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.
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.
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.
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.
andexanet alfa是一种针对Xa因子（FXa）抑制剂的特异性解毒剂，基于3期试验ANNEXA-4的结果，已在包括日本在内的多个国家获批用于临床。我们旨在评估andexanet alfa治疗日本参加ANNEXA-4试验的FXa抑制剂相关急性大出血患者的疗效和安全性。
这项预先设定的分析纳入了前瞻性、开放标签、单臂ANNEXA-4试验中日本研究点的患者。符合条件的患者在口服FXa抑制剂后18小时内发生大出血。共同主要疗效终点为治疗后12小时抗FXa活性的变化百分比以及达到优异或良好止血疗效的患者比例。
共纳入19例患者，均发生颅内出血；16例患者可进行疗效评估。服用阿哌沙班的患者从基线到最低点抗FXa活性的中位降低百分比为95.4%，服用利伐沙班的患者为96.1%，服用依度沙班的患者为82.2%。总体而言，14/16例患者（88%）实现了优异或良好的止血效果（阿哌沙班，5/5；利伐沙班，6/7；依度沙班，3/4）。在30天内，分别有2例和5例患者发生治疗相关不良事件（AE）和严重AE。1例患者在随访期间死亡，2例患者发生血栓事件。
andexanet alfa治疗可迅速降低日本急性大出血患者的抗FXa活性，并具有良好的止血疗效。与先前研究一样，在该人群中，抗FXa活性快速逆转期间发生血栓事件的严重AE是特别需要关注的安全问题。
