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用于静脉血栓栓塞管理的直接口服抗凝剂综合概述

A Comprehensive Overview of Direct Oral Anticoagulants for the Management of Venous Thromboembolism.

作者信息

Comerota Anthony J, Ramacciotti Eduardo

机构信息

Jobst Vascular Institute, ProMedical Health System, Toledo, Ohio.

Bristol-Myers Squibb Company, New York, New York.

出版信息

Am J Med Sci. 2016 Jul;352(1):92-106. doi: 10.1016/j.amjms.2016.03.018. Epub 2016 Apr 6.

Abstract

Venous thromboembolism (VTE) is a prevalent, potentially fatal health problem. Although standard anticoagulant therapy is effective when compared with the newer direct oral anticoagulants (DOACs), it has disadvantages. Heparin and its derivatives must be administered parenterally, whereas use of oral vitamin K antagonists is complicated by unpredictable pharmacokinetics and pharmacodynamics, drug-food and drug-drug interactions and the requirement for frequent laboratory monitoring. Randomized phase 3 trials have demonstrated that patients receive similarly effective anticoagulation with the DOACs dabigatran, edoxaban, rivaroxaban and apixaban when compared with warfarin, with similar or reduced risk of bleeding. Extended therapy trials have consistently demonstrated superior effectiveness for DOAC treatment when compared with placebo in preventing VTE recurrence. This article presents a comprehensive review of the pharmacokinetics, pharmacodynamics and accumulated clinical trial evidence for each DOAC for short-term, long-term and extended VTE therapy, and it considers the potential implications these agents have for the clinical management of VTE.

摘要

静脉血栓栓塞症(VTE)是一个普遍存在的、可能致命的健康问题。尽管与新型直接口服抗凝剂(DOACs)相比,标准抗凝治疗是有效的,但它也有缺点。肝素及其衍生物必须通过胃肠外途径给药,而口服维生素K拮抗剂的使用因不可预测的药代动力学和药效学、药物-食物及药物-药物相互作用以及频繁实验室监测的要求而变得复杂。随机3期试验已证明,与华法林相比,患者使用达比加群、依度沙班、利伐沙班和阿哌沙班等DOACs可获得同样有效的抗凝效果,且出血风险相似或降低。延长治疗试验一致表明,与安慰剂相比,DOAC治疗在预防VTE复发方面具有更高的有效性。本文全面综述了每种DOAC用于短期、长期和延长VTE治疗的药代动力学、药效学及累积临床试验证据,并探讨了这些药物对VTE临床管理的潜在影响。

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