anddexanet alfa：试验给我们留下了更多的问题。

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2025-01-01 DOI:10.1016/j.rpth.2024.102628

Richard J. Buka

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引用次数: 0

摘要

Andexanet Alfa在接受口服Xa因子抑制剂（ANNEXA-I）的急性颅内出血患者中的作用，这是有史以来第一个直接口服抗凝剂逆转剂的随机对照试验，于2024年发表。作为2018年有条件批准的一部分，该试验由美国食品和药物管理局（fda）授权，将颅内出血患者随机分配到andexanet或常规治疗中。该批准最初是基于单臂试验，the anddexanet Alfa，一种Xa因子抑制剂抗凝作用的新型解毒剂（ANNEXA-4）。为了获益，早期停止了ANNEXA-I，并显示明显血肿扩张的患者数量减少。然而，该研究没有为临床终点（如残疾或死亡）提供动力，并且这些结果没有显示差异。然而，它确实显示血栓形成的风险增加，主要是中风与阿德沙奈。从这个角度来看，我反思了对审判的一些关键批评及其解释的含义。

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Andexanet alfa: trials just leave us with more questions

Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor (ANNEXA-I), the first ever randomized controlled trial of a reversal agent for direct oral anticoagulants, was published in 2024. The trial, which randomized patients with intracranial hemorrhage to andexanet alfa or usual care, was mandated by the United States Food and Drug Administration as part of its conditional approval in 2018. This approval was originally based on the single-arm trial, The Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4). ANNEXA-I was stopped early for benefit and showed a reduction in the number of patients with significant hematoma expansion. However, the study was not powered for clinical endpoints such as disability or death and showed no difference in these outcomes. It did, however, show an increased risk of thrombosis, predominantly stroke with andexanet alfa. In this perspective, I reflect on some of the key criticisms of the trial and the implications for its interpretation.

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