Clinical and Safety Outcomes Associated With Treatment of Acute Venous Thromboembolism A Systematic Review and Meta-analysis
Clinical and Safety Outcomes Associated With Treatment of Acute Venous Thromboembolism A Systematic Review and Meta-analysis
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DOI：
10.1001/jama.2014.10538
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发表时间：
2014-09-17
影响因子：
120.7
通讯作者：
Carrier, Marc
中科院分区：
文献类型：
--
作者：
Castellucci, Lana A.;Cameron, Chris;Carrier, Marc
许多抗凝策略可用于治疗急性静脉血栓栓塞，但关于哪种药物最有效和安全的指导很少。目的总结和比较8种抗凝治疗方案（未分离肝素[UFH]、低分子肝素[LMWH]或fondaparinux联合维生素K拮抗剂）的疗效和安全性；低分子肝素加达比加群或依多沙班；rivaroxaban;apixaban;和低分子肝素单独)治疗静脉血栓栓塞。使用MEDLINE、EMBASE和2014年2月28日的循证医学综述进行系统的文献检索。研究选择：符合条件的研究是报告急性静脉血栓栓塞患者复发性静脉血栓栓塞和大出血发生率的随机试验。在确定的1197项研究中，45项试验包括44989名患者被纳入分析。两名评论者独立提取了试验水平的数据，包括患者数量、随访时间和结果。采用网络荟萃分析对数据进行汇总。主要临床结局和安全结局分别为静脉血栓栓塞复发和大出血。结果：与低分子肝素-维生素K拮抗剂联合治疗相比，ufh -维生素K拮抗剂联合治疗策略与静脉血栓栓塞复发风险增加相关（危险比[HR]， 1.42； 95%可信区间[CrI]， 1.15-1.79）。治疗3个月内静脉血栓栓塞复发的患者比例，ufh -维生素K拮抗剂联合组为1.84%(95% CrI, 1.33%-2.51%)， lmwh -维生素K拮抗剂联合组为1.30% （95% CrI, 1.02%-1.62%）。利伐沙班（HR, 0.55; 95% CrI, 0.35-0.89）和阿哌沙班（HR, 0.31; 95% CrI, 0.15-0.62）与低分子肝素-维生素K拮抗剂联合用药的出血风险较低，且在抗凝治疗3个月期间发生大出血事件的患者比例较低：利伐沙班为0.49% (95% CrI, 0.29%-0.85%)，阿哌沙班为0.28%(95% CrI, 0.14%-0.50%)，低分子肝素-维生素K拮抗剂联合用药为0.89%（95% CrI, 0.66%-1.16%）。结论和相关性荟萃分析显示，与低分子肝素-维生素K拮抗剂联合治疗相比，大多数用于治疗急性静脉血栓栓塞的治疗策略的疗效和安全性没有统计学差异。然而，研究结果表明，ufh -维生素K拮抗剂组合与最不有效的策略相关，利伐沙班和阿哌沙班可能与最低的出血风险相关。版权所有2014美国医学协会。版权所有。
IMPORTANCE Many anticoagulant strategies are available for the treatment of acute venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe.OBJECTIVE To summarize and compare the efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism.DATA SOURCES A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014.STUDY SELECTION Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism. Of the 1197 studies identified, 45 trials including 44 989 patients were included in the analyses.DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. The data were pooled using network meta-analysis.MAIN OUTCOMES AND MEASURES The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively.RESULTS Compared with the LMWH-vitamin K antagonist combination, a treatment strategy using the UFH-vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio [HR], 1.42; 95% credible interval [CrI], 1.15-1.79). The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84%(95% CrI, 1.33%-2.51%) for the UFH-vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%) for the LMWH-vitamin K antagonist combination. Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89) and apixaban (HR, 0.31; 95% CrI, 0.15-0.62) were associated with a lower risk of bleeding than was the LMWH-vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%) for rivaroxaban, 0.28%(95% CrI, 0.14%-0.50%) for apixaban, and 0.89%(95% CrI, 0.66%-1.16%) for the LMWH-vitamin K antagonist combination.CONCLUSIONS AND RELEVANCE Usingmeta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH-vitamin K antagonist combination. However, findings suggest that the UFH-vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding. Copyright 2014 American Medical Association. All rights reserved.