依达赛珠单抗在颅内出血中的止血效果和抗 FXa（因子 Xa）作用逆转：ANNEXA-4 子研究。
Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy.
机构信息
Departments of Clinical Neurosciences and Radiology, Cumming School of Medicine, University of Calgary, AB, Canada (A.M.D.).
Portola Pharmaceuticals, Inc, now Alexion Pharmaceuticals, Inc, South San Francisco, CA (P.Y., P.B.C., J.T.C.).
出版信息
Stroke. 2021 Jun;52(6):2096-2105. doi: 10.1161/STROKEAHA.120.030565. Epub 2021 May 10.
BACKGROUND AND PURPOSE
Andexanet alfa is a recombinant modified human FXa (factor Xa) developed to reverse FXa inhibition from anticoagulants. Hemostatic efficacy and reversal of anti-FXa activity with andexanet were assessed in patients from the ANNEXA-4 study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors) with intracranial hemorrhage (ICrH).
METHODS
ANNEXA-4 was a single-arm study evaluating andexanet in patients presenting with major bleeding ≤18 hours after taking an FXa inhibitor. Patients received a bolus plus 2-hour infusion of andexanet. Brain imaging in patients with ICrH was performed at baseline and at 1 and 12 hours postandexanet infusion. Coprimary efficacy outcomes were change in anti-FXa activity and hemostatic efficacy at 12 hours (excellent/good efficacy defined as ≤35% increase in hemorrhage volume/thickness). Safety outcomes included occurrence of thrombotic events and death at 30 days.
RESULTS
A total of 227 patients with ICrH were included in the safety population (51.5% male; mean age 79.3 years) and 171 in the efficacy population (99 spontaneous and 72 traumatic bleeds). In efficacy evaluable patients, excellent/good hemostasis 12 hours postandexanet occurred in 77 out of 98 (78.6%) and in 58 out of 70 (82.9%) patients with spontaneous and traumatic bleeding, respectively. In the subanalysis by FXa inhibitor treatment group in the efficacy population, median of percent change in anti-FXa from baseline to nadir showed a decrease of 93.8% for apixaban-treated patients (n=99) and by 92.6% for rivaroxaban-treated patients (n=59). Within 30 days, death occurred in 34 out of 227 (15.0%) patients and thrombotic events occurred in 21 out of 227 (9.3%) patients (safety population).
CONCLUSIONS
Andexanet reduced anti-FXa activity in FXa inhibitor-treated patients with ICrH, with a high rate of hemostatic efficacy. Andexanet may substantially benefit patients with ICrH, the most serious complication of anticoagulation.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT02329327.
背景与目的
Andexanet alfa 是一种重组改良的人 FXa（因子 Xa），旨在逆转抗凝剂对 FXa 的抑制作用。在颅内出血（ICH）患者中，通过 ANNEXA-4 研究（Andexanet Alfa，一种新型抗 FXa 抑制剂抗凝作用的解毒剂）评估了 andexanet 的止血效果和抗 FXa 活性的逆转。
方法
ANNEXA-4 是一项单臂研究，评估了在接受 FXa 抑制剂治疗后 18 小时内发生主要出血的患者使用 andexanet 的情况。患者接受 andexanet 推注加 2 小时输注。ICH 患者在基线时和输注 andexanet 后 1 小时和 12 小时进行脑部成像。主要疗效终点是 12 小时时抗 FXa 活性和止血效果的变化（优秀/良好疗效定义为出血体积/厚度增加≤35%）。安全性结局包括 30 天内血栓形成事件和死亡的发生。
结果
共有 227 例 ICrH 患者进入安全性人群（51.5%为男性；平均年龄 79.3 岁），171 例进入疗效人群（99 例自发性出血和 72 例创伤性出血）。在可评估疗效的患者中，98 例中有 77 例（78.6%）和 70 例中有 58 例（82.9%）患者在接受 andexanet 治疗 12 小时后止血效果良好。在疗效人群的 FXa 抑制剂治疗组亚分析中，接受阿哌沙班治疗的患者（n=99）的抗 FXa 从基线到最低点的百分比变化中位数下降了 93.8%，接受利伐沙班治疗的患者（n=59）下降了 92.6%。在 30 天内，227 例患者中有 34 例（15.0%）死亡，227 例患者中有 21 例（9.3%）发生血栓形成事件（安全性人群）。
结论
Andexanet 降低了 ICrH 中接受 FXa 抑制剂治疗的患者的抗 FXa 活性，止血效果良好。Andexanet 可能使 ICrH 患者显著受益，ICH 是抗凝最严重的并发症。
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