Comparison of the Novel Oral Anticoagulants Apixaban, Dabigatran, Edoxaban, and Rivaroxaban in the Initial and Long-Term Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis.
Comparison of the Novel Oral Anticoagulants Apixaban, Dabigatran, Edoxaban, and Rivaroxaban in the Initial and Long-Term Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis.
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DOI：
10.1371/journal.pone.0144856
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Batson S
中科院分区：
文献类型：
--
作者：
Cohen AT;Hamilton M;Mitchell SA;Phatak H;Liu X;Bird A;Tushabe D;Batson S
使用低分子量肝素和维生素 K 拮抗剂抗凝是目前治疗和预防静脉血栓栓塞 (VTE) 的护理标准 (SOC)。尽管新型口服抗凝剂 (NOAC) 已在该适应症中与 SOC 进行了比较，但尚无直接比较 NOAC 的头对头随机对照试验 (RCT)。进行了系统评价和网络荟萃分析 (NMA)，以比较 NOAC 对 VTE 初始和长期治疗的疗效和安全性。系统地检索了电子数据库（2014 年 7 月访问），以确定评估阿哌沙班、达比加群、依度沙班和利伐沙班与 SOC 的随机对照试验。符合条件的患者包括客观证实患有深静脉血栓（DVT）、肺栓塞（PE）或两者兼而有之的成年人。对感兴趣的结果进行固定效应贝叶斯 NMA，结果以相对风险 (RR) 和 95% 可信区间 (Crl) 表示。六项 III 期随机对照试验符合纳入标准：阿哌沙班（一项随机对照试验；n = 5,395）；利伐沙班（两项随机对照试验；n = 3,423/4,832）；达比加群（两项随机对照试验；n = 2,539/2,568）；艾多沙班（一项随机对照试验；n = 8,240）。 NOAC 之间在“VTE 风险”和“VTE 相关死亡”方面没有统计学上的显着差异。阿哌沙班治疗与 NOAC 中最有利的安全性相关，与利伐沙班 (0.47 [0.36，0.61])、达比加群 (0.69 [0.51，0.94]) 和艾多沙班 (0.54 [0.41， 0.69]）。与利伐沙班 (0.68 [0.53, 0.87]) 和艾多沙班 (0.77 [0.60, 0.99]) 相比，达比加群还与“大出血或 CRNM 出血”风险显着降低相关。间接比较显示，所有 NOAC 的“VTE 或 VTE 相关死亡风险”的降低具有统计学相似性。相比之下，与所有其他 NOAC 相比，阿哌沙班在初始/长期治疗中显着更好地减少了“大出血或 CRNM 出血”，而与利伐沙班和依多沙班相比，达比加群则显着更好。目前的分析结果表明，NOAC 比传统疗法具有临床益处，同时突出了其出血情况的相对差异。
Anticoagulation with low molecular weight heparin and vitamin K antagonists is the current standard of care (SOC) for venous thromboembolism (VTE) treatment and prevention. Although novel oral anti-coagulants (NOACs) have been compared with SOC in this indication, no head-to-head randomised controlled trials (RCTs) have directly compared NOACs. A systematic review and network meta-analysis (NMA) were conducted to compare the efficacy and safety of NOACs for the initial and long-term treatment of VTE. Electronic databases (accessed July 2014) were systematically searched to identify RCTs evaluating apixaban, dabigatran, edoxaban, and rivaroxaban versus SOC. Eligible patients included adults with an objectively confirmed deep vein thrombosis (DVT), pulmonary embolism (PE) or both. A fixed-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as relative risks (RR) and 95% credible intervals (Crl). Six Phase III RCTs met criteria for inclusion: apixaban (one RCT; n = 5,395); rivaroxaban (two RCTs; n = 3,423/4,832); dabigatran (two RCTs; n = 2,539/2,568); edoxaban (one RCT; n = 8,240). There were no statistically significant differences between the NOACs with regard to the risk of ‘VTE and VTE-related death. Apixaban treatment was associated with the most favourable safety profile of the NOACs, showing a statistically significantly reduced risk of ‘major or clinically relevant non-major (CRNM) bleed’ compared with rivaroxaban (0.47 [0.36, 0.61]), dabigatran (0.69 [0.51, 0.94]), and edoxaban (0.54 [0.41, 0.69]). Dabigatran was also associated with a significantly lower risk of ‘major or CRNM bleed’ compared with rivaroxaban (0.68 [0.53, 0.87]) and edoxaban (0.77 [0.60, 0.99]). Indirect comparisons showed statistically similar reductions in the risk of ‘VTE or VTE-related death for all NOACs. In contrast, reductions in ‘major or CRNM bleed’ for initial/long-term treatment were significantly better with apixaban compared with all other NOACs, and with dabigatran compared with rivaroxaban and edoxaban. Results from the current analysis indicate that the NOACs offer clinical benefit over conventional therapy while highlighting relative differences in their bleeding profile.