University of Connecticut School of Pharmacy, Department of Pharmacy Practice, 69 North Eagleville Rd Unit 3092, Storrs, CT 06269, USA.
Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Thromb Res. 2015 May;135(5):888-96. doi: 10.1016/j.thromres.2015.02.032. Epub 2015 Mar 4.
To systematically review the literature and to quantitatively evaluate the efficacy and safety of extended pharmacologic treatment of venous thromboembolism (VTE) through network meta-analysis (NMA).
A systematic literature search (MEDLINE, Embase, Cochrane CENTRAL, through September 2014) and searching of reference lists of included studies and relevant reviews was conducted to identify randomized controlled trials of patients who completed initial anticoagulant treatment for VTE and then randomized for the extension study; compared extension of anticoagulant treatment to placebo or active control; and reported at least one outcome of interest (VTE or a composite of major bleeding or clinically relevant non-major bleeding). A random-effects Frequentist approach to NMA was used to calculate relative risks with 95% confidence intervals.
Ten trials (n=11,079) were included. Risk of bias (assessed with the Cochrane tool) was low in most domains assessed across the included trials. Apixaban (2.5mg and 5mg), dabigatran, rivaroxaban, idraparinux and vitamin K antagonists (VKA) each significantly reduced the risk of VTE recurrence compared to placebo, ranging from a 73% reduction with idraparinux to 86% with VKAs. With exception of idraparinux, all active therapies significantly reduced VTE recurrence risk versus aspirin, ranging from a 73% reduction with either apixaban 2.5mg or rivaroxaban to 80% with VKAs. Apixaban and aspirin were the only therapies that did not increase composite bleeding risk significantly compared to placebo. All active therapies except aspirin increased risk of composite bleeding by 2 to 4-fold compared to apixaban 2.5mg, with no difference found between the two apixaban doses.
Extended treatment of VTE is a reasonable approach to provide continued protection from VTE recurrence although bleeding risk is variable across therapeutic options. Our results indicate that apixaban, dabigatran, rivaroxaban, idraparinux and VKAs all reduced VTE recurrence when compared to placebo. Apixaban appears to have a more favorable safety profile compared to other therapies.
通过网络荟萃分析（NMA）系统地回顾文献并定量评估静脉血栓栓塞症（VTE）的延长药物治疗的疗效和安全性。
对 MEDLINE、Embase、Cochrane 中心数据库（截至 2014 年 9 月）进行了系统的文献检索，并对纳入研究的参考文献列表和相关综述进行了检索，以确定完成 VTE 初始抗凝治疗后随机进入扩展研究的患者的随机对照试验；比较了抗凝治疗的扩展与安慰剂或活性对照；并报告了至少一个感兴趣的结局（VTE 或大出血或临床相关非大出血的复合结局）。采用随机效应 Frequentist 方法进行 NMA 计算，以计算相对风险及其 95%置信区间。
纳入了 10 项试验（n=11079）。纳入的试验中，大多数评估领域的偏倚风险（采用 Cochrane 工具评估）均较低。与安慰剂相比，阿哌沙班（2.5mg 和 5mg）、达比加群、利伐沙班、依达肝素和维生素 K 拮抗剂（VKA）均显著降低 VTE 复发风险，风险降低幅度从依达肝素的 73%到 VKA 的 86%不等。除依达肝素外，与阿司匹林相比，所有活性治疗药物均显著降低 VTE 复发风险，风险降低幅度从阿哌沙班 2.5mg 或利伐沙班的 73%到 VKA 的 80%不等。与安慰剂相比，只有阿哌沙班和阿司匹林没有显著增加复合出血风险。与阿哌沙班 2.5mg 相比，除阿司匹林外，所有活性治疗药物均使复合出血风险增加 2 至 4 倍，但两种阿哌沙班剂量之间无差异。
尽管治疗选择的出血风险存在差异，但 VTE 的延长治疗是一种合理的方法，可以持续提供对 VTE 复发的保护。我们的研究结果表明，与安慰剂相比，阿哌沙班、达比加群、利伐沙班、依达肝素和 VKA 均降低了 VTE 的复发率。与其他治疗方法相比，阿哌沙班似乎具有更好的安全性。
