利伐沙班与依诺肝素用于恶性肿瘤合并静脉血栓栓塞症疗效与安全性比较的Meta分析

张亚同 车宁 朱翊 李铮 李鸿升 胡欣

摘 要 目的：比较利伐沙班与依诺肝素用于恶性肿瘤合并静脉血栓栓塞症的疗效与安全性，为临床用药提供循证参考。方法：计算机检索PubMed、Embase、Cochrane图书馆、Clinical Trials、中国期刊全文数据库、中国生物医学文献数据库、维普网等数据库，收集利伐沙班对比依诺肝素的临床试验或观察性研究，检索时限均为各数据库建库起至2020年4月。筛选文献、提取数据后，采用纽卡斯尔-渥太华量表对纳入文献质量进行评价，采用Stata 15.0软件进行Meta分析、敏感性分析、发表偏倚分析。结果：共纳入5项观察性单中心队列研究，其中4项为回顾性队列研究、1项为前瞻性队列研究;共计997例患者，其中625例接受依诺肝素治疗、372例接受利伐沙班治疗。Meta分析结果显示，两组患者随访3个月时[RR=0.91，95%CI（0.50，1.66），P=0.760]、随访6个月时[RR=0.53，95%CI（0.24，1.15），P=0.106]静脉血栓栓塞症复发率及随访3个月时[RR=1.22，95%CI（0.66，2.25），P=0.530]、随访6个月时[RR=1.30，95%CI（0.73，2.33），P=0.368]大出血发生率比较，差异均无统计学意义。敏感性分析结果显示，上述Meta分析结果较稳健;发表偏倚分析结果显示，本研究存在发表偏倚的可能性较小。结论：利伐沙班用于恶性肿瘤合并静脉血栓栓塞症的疗效和安全性与依诺肝素相当。

关键词 利伐沙班;依诺肝素;恶性肿瘤;静脉血栓栓塞症;疗效;安全性;Meta分析

ABSTRACT   OBJECTIVE： To compare the efficacy and safety of rivaroxaban versus enoxaparin in the treatment of malignant tumor complicated with venous thromboembolism （VTE）， and to provide evidence-based reference to the clinic. METHODS： Retrieved from PubMed， Embase， Cochrane Library， Clinical Trials， CNKI， CBM and VIP， clinical trials or observational studies about rivaroxaban versus enoxaparin were collected during the inception to Apr. 2020. After literature screening and data extraction， the quality of included literatures were evaluated by Newcastle Ottawa scale; Stata 15.0 software was used to conduct Meta-analysis， sensitivity analysis and publication bias analysis. RESULTS： A total of 5 observational clinical cohort studies were retrieved， including 4 retrospective cohort studies and one prospective cohort study. Totally 997 patients were included， among which 625 patients received enoxaparin and 372 patients received rivaroxaban. Results of Meta-analysis showed that there was no statistical significance in recurrence rate of VTE at 3 months follow-up [RR=0.91，95%CI （0.50，1.66），P=0.760] and 6 months follow-up [RR=0.53，95%CI（0.24，1.15），P=0.106] as well as the incidence of massive hemorrhage at 3 months follow-up [RR=1.22 ，95%CI（0.66，2.25），P=0.530] and 6 months follow-up [RR=1.30，95%CI（0.73，2.33），P=0.368]. The results of sensitivity analysis showed that the results of above Meta-analysis were stable; the results of publication bias analysis showed that there was less possibility of publication bias in this study. CONCLUSIONS： Rivaroxaban is as effective and safe as enoxaparin in the treatment of malignant tumor with VTE.

KEYWORDS   Rivaroxaban; Enoxaparin; Malignant cancer; Venous thromboembolism; Efficacy; Safety; Meta-analysis

靜脉血栓栓塞症（VTE）是一种常见的肿瘤合并症。约10%～20%的VTE患者患有活动性肿瘤或有肿瘤病史[1]。在肿瘤合并VTE患者的预防和治疗中，证据级别最高、研究最充分的是各种低分子量肝素（LMWH）[2]。LMWH是由普通肝素解聚制备而成的一类分……