Department of Medicine, the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
JAMA. 2014 Sep 17;312(11):1122-35. doi: 10.1001/jama.2014.10538.
Many anticoagulant strategies are available for the treatment of acute venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe.
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.
A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014.
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.
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.
The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively.
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.
Using meta-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.
重要性：急性静脉血栓栓塞症的治疗方法有很多种抗凝策略，但哪种药物最有效和安全，几乎没有指导意见。
目的：总结和比较 8 种抗凝选择（未分馏肝素[UFH]、低分子量肝素[LMWH]或磺达肝癸钠联合维生素 K 拮抗剂）；LMWH 联合达比加群或依度沙班；利伐沙班；阿哌沙班；LMWH 单药）治疗静脉血栓栓塞的疗效和安全性结局。
数据来源：通过 MEDLINE、EMBASE 和循证医学综述，从成立到 2014 年 2 月 28 日进行了系统的文献检索。
研究选择：合格的研究是随机试验，报告了急性静脉血栓栓塞患者的复发性静脉血栓栓塞和大出血的发生率。在确定的 1197 项研究中，包括 44989 名患者的 45 项试验被纳入分析。
数据提取和综合：两位评审员独立提取了包括患者人数、随访时间和结局在内的试验水平数据。使用网络荟萃分析对数据进行汇总。
主要结果和测量：主要的临床和安全性结局分别是复发性静脉血栓栓塞和大出血。
结果：与 LMWH-维生素 K 拮抗剂联合治疗相比，使用 UFH-维生素 K 拮抗剂联合治疗策略与复发性静脉血栓栓塞的风险增加相关（危险比[HR]，1.42；95%可信区间[CrI]，1.15-1.79）。在 3 个月的治疗期间，发生复发性静脉血栓栓塞的患者比例分别为：UFH-维生素 K 拮抗剂联合治疗组为 1.84%（95%CrI，1.33%-2.51%），LMWH-维生素 K 拮抗剂联合治疗组为 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）与较低的出血风险相关，在 3 个月的抗凝治疗期间，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%），LMWH-维生素 K 拮抗剂联合治疗组为 0.89%（95%CrI，0.66%-1.16%）。
结论和相关性：使用荟萃分析汇总，与 LMWH-维生素 K 拮抗剂联合治疗相比，大多数治疗急性静脉血栓栓塞的策略在疗效和安全性方面没有统计学上的显著差异。然而，研究结果表明，UFH-维生素 K 拮抗剂联合治疗策略的效果最差，利伐沙班和阿哌沙班可能与出血风险最低相关。
