癌症患者静脉血栓栓塞的治疗：不同直接口服抗凝剂（DOACs）疗效和安全性的系统评价与荟萃分析
Treatment of venous thromboembolism in cancer patients: a systematic review and meta-analysis on the efficacy and safety of different direct oral anticoagulants (DOACs).
作者信息
Song Xiaojun, Liu Zhili, Zeng Rong, Shao Jiang, Liu Bao, Zheng Yuehong, Liu Changwei, Ye Wei
机构信息
Department of Vascular Surgery, Peking Union Medical College Hospital, Beijing, China.
出版信息
Ann Transl Med. 2021 Jan;9(2):162. doi: 10.21037/atm-20-8156.
BACKGROUND
To evaluate the efficacy and safety of different direct oral anticoagulants (DOACs) compared with low molecular weight heparins (LMWHs) in the treatment of venous thromboembolism (VTE) in cancer patients.
METHODS
Literature was searched in databases including Cochrane Library, EMBASE (Ovid), and MEDLINE (PubMed). Eligible studies were included, and data were collected independently by 2 reviewers. We conducted a systematic review of the efficacy and safety of DOACs in the treatment of VTE in cancer patients. The odds ratios (ORs) of different DOACs compared with LMWHs for VTE, deep vein thrombosis (DVT), pulmonary embolism (PE) recurrence, major bleeding, and clinically relevant non-major bleeding (CRNMB), were calculated in meta-analyses and subgroup analyses.
RESULTS
A total of 18 articles were eligible for analyses, including 4 randomized controlled trials (RCTs) and 14 retrospective studies. Both RCTs and retrospective studies confirmed that DOACs decreased the risk of VTE recurrence [RCTs: OR, 0.60; 95% confidence interval (CI), 0.45-0.80; retrospective studies: OR, 0.73; 95% CI, 0.59-0.90] and DVT recurrence (RCTs: OR, 0.54; 95% CI, 0.36-0.80; retrospective studies: OR, 0.20; 95% CI, 0.06-0.63), but not PE recurrence or fatal PE in cancer patients. Subgroup analyses revealed an important role of rivaroxaban in decreasing recurrent VTE. Meanwhile, major bleeding events were not increased in the DOAC group, but the risks of CRNMBs were significantly elevated. Subgroup analyses confirmed the role of rivaroxaban in increasing the risk of major bleeding events and CRNMBs.
CONCLUSIONS
Compared with LMWHs, DOACs (especially rivaroxaban) significantly reduce the risk of VTE and DVT, but not PE recurrence, in patients with cancer. Although DOACs did not increase the major bleeding events in pooled analysis, rivaroxaban showed an elevated risk of this adverse effect in subgroup analysis. In addition, the risk of CRNMB events was increased after the application of DOACs including rivaroxaban.
背景
评估不同直接口服抗凝剂（DOACs）与低分子肝素（LMWHs）相比，在治疗癌症患者静脉血栓栓塞症（VTE）中的疗效和安全性。
方法
在包括Cochrane图书馆、EMBASE（Ovid）和MEDLINE（PubMed）在内的数据库中检索文献。纳入符合条件的研究，由2名评审员独立收集数据。我们对DOACs治疗癌症患者VTE的疗效和安全性进行了系统评价。在荟萃分析和亚组分析中，计算了不同DOACs与LMWHs相比，VTE、深静脉血栓形成（DVT）、肺栓塞（PE）复发、大出血和临床相关非大出血（CRNMB）的比值比（ORs）。
结果
共有18篇文章符合分析条件，包括4项随机对照试验（RCTs）和14项回顾性研究。RCTs和回顾性研究均证实，DOACs降低了VTE复发风险[RCTs：OR，0.60；95%置信区间（CI），0.45 - 0.80；回顾性研究：OR，0.73；95%CI，0.59 - 0.90]和DVT复发风险（RCTs：OR，0.54；95%CI，0.36 - 0.80；回顾性研究：OR，0.20；95%CI，0.06 - 0.63），但未降低癌症患者的PE复发或致命PE风险。亚组分析显示利伐沙班在降低复发性VTE方面具有重要作用。同时，DOAC组大出血事件未增加，但CRNMB风险显著升高。亚组分析证实了利伐沙班在增加大出血事件和CRNMB风险方面的作用。
结论
与LMWHs相比，DOACs（尤其是利伐沙班）显著降低了癌症患者VTE和DVT的风险，但未降低PE复发风险。虽然在汇总分析中DOACs未增加大出血事件，但在亚组分析中利伐沙班显示出这种不良反应的风险升高。此外，包括利伐沙班在内的DOACs应用后CRNMB事件风险增加。
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