Martínez-Zapata M José, Mathioudakis Alexander G, Mousa Shaker A, Bauersachs Rupert
1 Public Health and Clinical Epidemiology Service, Instituto de Investigación Biomédica Sant Pau, CIBERESP, Barcelona, Spain.
2 Division of Infection, Immunity and Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, University of Manchester, Manchester, United Kingdom.
Clin Appl Thromb Hemost. 2018 Mar;24(2):226-234. doi: 10.1177/1076029617696581. Epub 2017 Mar 14.
Patients with cancer are at increased risk of recurrent venous thromboembolism (VTE) and bleeding. Thus, long-term treatment with anticoagulants for secondary prevention is challenging. The objective of this review was to evaluate current evidence on the safety and efficacy of tinzaparin compared with other anticoagulants for long-term VTE treatment in patients with cancer. Based on a preregistered protocol, we identified randomized controlled trials (RCTs) comparing long-term tinzaparin (therapeutic dose: 175 IU/kg) versus other anticoagulants for at least 3 months after an acute episode of VTE that included adult patients with underlying malignancy. We extracted predefined, clinically relevant outcomes of patients with cancer and, using standard methodology, pooled available data and assessed risk of bias and quality of evidence for each study. Three open-label RCTs evaluating 1169 patients with cancer were included in the analysis. Tinzaparin was associated with a significantly lower risk of recurrent VTE at the end of treatment (relative risk [RR], [95% confidence interval] 0.67 [0.46-0.99]) and at longest follow-up (RR: 0.58 [0.39-0.88]) and showed a lower risk of clinically relevant non-major bleeding at the end of treatment (RR: 0.71 [0.51-1.00]). No significant between-treatment differences were found for all-cause mortality (RR: 1.09 [0.91-1.30]) or fatal and non-fatal major bleeding events (RR: 1.06 [0.56-1.99]). The overall quality of evidence was deemed moderate, mainly due to small sample size in 2 of the studies and limited number of events in the meta-analyses. In conclusion, both short- and long-term treatments with tinzaparin were found to be superior to vitamin K antagonists for avoiding recurrences of VTE.
癌症患者发生复发性静脉血栓栓塞（VTE）和出血的风险增加。因此，使用抗凝剂进行二级预防的长期治疗具有挑战性。本综述的目的是评估与其他抗凝剂相比，替扎肝素用于癌症患者长期VTE治疗的安全性和有效性的现有证据。根据预先注册的方案，我们纳入了比较急性VTE发作后至少3个月长期使用替扎肝素（治疗剂量：175 IU/kg）与其他抗凝剂的随机对照试验（RCT），其中包括患有潜在恶性肿瘤的成年患者。我们提取了癌症患者预先定义的、临床相关的结局，并使用标准方法汇总可用数据，评估每项研究的偏倚风险和证据质量。分析纳入了3项评估1169例癌症患者的开放标签RCT。替扎肝素在治疗结束时（相对风险[RR]，[95%置信区间]0.67[0.46 - 0.99]）和最长随访时（RR：0.58[0.39 - 0.88]）复发性VTE风险显著较低，且在治疗结束时临床相关非大出血风险较低（RR：0.71[0.51 - 1.00]）。在全因死亡率（RR：1.09[0.91 - 1.30]）或致命和非致命大出血事件（RR：1.06[0.56 - 1.99]）方面未发现显著的治疗组间差异。证据的总体质量被认为是中等的，主要是由于其中2项研究的样本量较小以及荟萃分析中的事件数量有限。总之，发现替扎肝素的短期和长期治疗在避免VTE复发方面均优于维生素K拮抗剂。
