OBJECTIVE To explore the efficacy and safety of direct oral factor Xa inhibitors in the treatment of cancer-associated acute venous thromboembolism (VTE). PATIENTS AND METHODS MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Embase databases were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer-associated acute VTE. Databases were searched from inception to September 19, 2018. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence and major and clinically relevant nonmajor bleeding. RESULTS We identified 3 randomized controlled trials, at low risk of bias, that enrolled 1739 patients with cancer-associated VTE. Direct comparison revealed a lower rate of VTE recurrence in DOAC compared with dalteparin groups (odds ratio [OR], 0.48; 95% CI, 0.24-0.96; I2=46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared with dalteparin (OR, 0.10; 95% CI, 0.01-0.82) but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared with dalteparin (OR, 1.70; 95% CI, 1.04-2.78). Clinically relevant nonmajor bleeding did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding, whereas estimates in urothelial cancer were imprecise. CONCLUSION Direct oral anticoagulants appear to lower the risk of VTE recurrence compared with dalteparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared with the other DOACs.

中文翻译：

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直接口服因子Xa抑制剂治疗急性癌症相关的静脉血栓栓塞症：系统评价和网络Meta分析。

目的探讨直接口服Xa因子抑制剂在治疗癌症相关的急性静脉血栓栓塞症（VTE）中的疗效和安全性。病人和方法检​​索MEDLINE，CENTRAL（对照试验的Cochrane中央登记册）和Embase数据库，以比较直接口服抗凝剂（DOAC）和达肝素治疗癌症相关的急性VTE的试验。搜索数据库从开始到2018年9月19日。使用频度和贝叶斯方法进行网络荟萃分析，以分析VTE复发以及主要和临床相关的非主要出血。结果我们确定了3项偏倚风险较低的随机对照试验，该试验招募了1739例癌症相关性VTE患者。直接比较显示，DOAC中的VTE复发率比达肝素组低（几率[OR]为0.48； 95％CI为0.24-0.96； I2 = 46％）。间接比较表明，与达肝素相比，阿哌沙班的VTE复发降低幅度更大（OR为0.10； 95％CI为0.01-0.82），但利伐沙班或依多沙班则没有。阿哌沙班也被评为最有效的可能性最高。通过直接比较，与达肝素相比，DOAC组发生大出血的可能性增加（OR为1.70； 95％CI为1.04-2.78）。临床相关的非重大出血没有差异。间接估计不准确。胃肠道癌的亚组分析表明，达肝素可能具有最低的出血风险，而尿路上皮癌的估计是不准确的。结论与达肝素相比，直接口服抗凝药似乎降低了VTE复发的风险，同时增加了大出血量。与其他DOAC相比，阿哌沙班的VTE复发风险最低。