Development of apixaban: a novel anticoagulant for prevention of stroke in patients with atrial fibrillation.
Development of apixaban: a novel anticoagulant for prevention of stroke in patients with atrial fibrillation.
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DOI：
10.1111/nyas.12567
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发表时间：
2014-11
影响因子：
5.2
通讯作者：
Lawrence JH
中科院分区：
文献类型：
--
作者：
Hanna MS;Mohan P;Knabb R;Gupta E;Frost C;Lawrence JH
Xa因子抑制剂阿哌沙班是一种新型抗凝剂，可替代长期使用的标准治疗，包括低分子量肝素和华法林。阿哌沙班的开发反映了一种优化临床药理学特征、剂量学、试验设计和多种适应症的统计分析，并寻求与全球卫生当局保持一致的策略。剂量选择的主要目的是维持疗效和出血风险之间的平衡。选择阿哌沙班每日两次给药，而不是每日一次，以降低峰浓度并减少峰和谷水平之间的波动。我们在这里讨论的重点是阿哌沙班用于预防非瓣膜性房颤（NVAF）的卒中。为了支持这一适应症，进行了一对登记试验，招募了根据指南符合抗凝治疗条件的全谱患者。在对不适合华法林治疗的患者进行的AVERROES研究中，阿哌沙班在降低卒中或全身栓塞（SSE）风险方面优于阿司匹林（上级），而不会显著增加大出血（MB）。在ARISTOTLE（阿哌沙班用于减少房颤患者的卒中和其他血栓性事件）研究中，阿哌沙班在SSE、MB和全因死亡率方面优于华法林，且具有上级优势。总体而言，这些研究已证明，在NVAF中，阿哌沙班的获益-风险特征显著优于华法林和阿司匹林。
The factor Xa inhibitor apixaban is one of the novel anticoagulants to emerge as alternatives to long-standing standards of care that include low-molecular-weight heparin and warfarin. The development of apixaban reflects a strategy to optimize the clinical pharmacology profile, dosing posology, trial designs, and statistical analyses across multiple indications, and to seek alignment with global health authorities. The primary objective of dose selection was to maintain balance between efficacy and bleeding risk. Twice-daily dosing of apixaban, rather than once daily, was chosen to lower peak concentrations and reduce fluctuations between peak and trough levels. Our discussion here focuses on the use of apixaban for stroke prevention in nonvalvular atrial fibrillation (NVAF). Supporting this indication, a pair of registrational trials was conducted that enrolled the full spectrum of patients who, by guidelines, were eligible for anticoagulation. In the AVERROES study of patients who were unsuitable for warfarin therapy, apixaban was superior to aspirin in reducing the risk of stroke or systemic embolism (SSE), without a significant increase in major bleeding (MB). In the ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) study, apixaban was superior to warfarin on the rates of SSE, MB, and all-cause mortality. Overall, these studies have demonstrated a substantially favorable benefit–risk profile for apixaban over warfarin and aspirin in NVAF.
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