新型口服抗凝药治疗静脉血栓栓塞症:试验序贯分析和网状Meta分析  

Treatment of venous thromboembolism with new oral anticoagulants:A trial sequential analysis and network Meta-analysis

作　　者：曹璐 王岩[3] 张颖[3] 张涛 董亚琳[3] 邢建峰[1] CAO Lu;WANG Yan;ZHANG Ying;ZHANG Tao;DONG Ya-lin;XING Jian-feng(School of Pharmacy,Xi'an Jiaotong University,Xi'an 710061;Beiguan Community Health Service Center,Lianhu District,Xi'an 710015;Department of Pharmacy,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061)

机构地区：[1]西安交通大学药学院,西安710061 [2]莲湖区北关社区卫生服务中心,西安710015 [3]西安交通大学第一附属医院药学部,西安710061

出　　处：《中南药学》2020年第2期292-299,共8页Central South Pharmacy

摘　　要：目的系统综合评价新型口服抗凝药物应用于治疗静脉血栓栓塞症(VTE)的有效性和安全性。方法计算机检索PubMed、Embase、Cochrane、ClinicalTrials.gov数据库,检索时限为建库至2018年12月。检索关于对比新型口服抗凝药与华法林治疗差异的随机对照研究,根据纳入和排除标准由两名研究者独立进行文献筛选、数据提取及质量评价,使用Stata 13.0软件和TSA v0.9.5.10对数据进行网状Meta分析和试验序贯分析(TSA)。结果共纳入符合标准的9项随机对照研究,总计27314例患者,涉及5种口服抗凝药(华法林、达比加群、阿哌沙班、利伐沙班、依度沙班)。网状Meta分析结果显示:①新型口服抗凝药在复发性VTE或VTE相关死亡率上差异无统计学意义;②在降低严重出血率上阿哌沙班显著优于达比加群[OR=2.54,95%CI(1.23,5.23)]和依度沙班[OR=2.84,95%CI(1.45,5.57)];③在降低临床相关的非严重出血率上阿哌沙班显著优于依度沙班[OR=1.75,95%CI(1.32,2.34)]和利伐沙班[OR=0.45,95%CI(0.34,0.60)],达比加群显著优于依度沙班[OR=1.37,95%CI(1.01,1.84)]和利伐沙班[OR=0.58,95%CI(0.43,0.79)];④各新型口服抗凝药在全因死亡率指标上差异没有统计学意义。此外,TSA分析表明,结局指标中复发性VTE或VTE相关死亡率和全因死亡率的Meta分析结果稳定、可靠;严重出血和临床相关的非严重出血率因样本量不足,存在假阳性可能。结论综合比较新型口服抗凝药的有效性和安全性,阿哌沙班在所有结局指标中排序均为最佳,可作为临床治疗VTE的优选药物。相比维生素K拮抗剂华法林,新型口服抗凝药是否在严重和临床相关的非严重出血率等安全性方面具有优势仍需更多的临床研究。Objective To determine the efficacy and safety of new oral anticoagulants(NOACs)for venous thromboembolism(VTE)systematically.Methods A systematic literature search of PubMed,Embase,Cochrane,and ClinicalTrials.gov till December 2018 was performed to identify randomized controlled trials(RCTs)regarding new oral anticoagulants for VTE.Two investigators screened the literatures according to eligibility criteria,and assessed the quality of included studies independently.Then,a random-effect model was used with trial sequential analyses(TSA).A network Meta-analysis(NMA)was conducted to obtain indirect evidence.Results Nine RCTs met the criteria,including 27314 patients and 5 oral anticoagulants(warfarin,dabigatran,apixaban,rivaroxaban,and edoxaban).The network meat-analysis showed that:①no statistical significant differences were found between the NOACs with regard to the risk of VTE and VTE-related deaths;②apixaban significantly reduced the major bleeding rates compared with dabigatran[OR=2.54,95%CI(1.23,5.23)]and edoxaban[OR=2.84,95%CI(1.45,5.57)];③apixaban significantly reduced clinically relevant non-major(CRNM)bleeding rates,more than edoxaban[OR=1.75,95%CI(1.32,2.34)]and rivaroxaban[OR=0.45,95%CI(0.34,0.60)],and dabigatran much better than edoxaban[OR=1.37,95%CI(1.01,1.84)]and rivaroxaban[OR=0.58,95%CI(0.43,0.79)];④there was no significant difference between the NOACs for the all-cause mortality.Moreover,TSA indicated that Meta-analysis of recurrent VTE or VTE-related deaths and all-cause mortality was reliable and conclusive.The sample of the major bleeding and CRNM bleeding rates was inadequate,and false positive might exist.Conclusion The efficacy and safety of NOACs are comprehensively compared.Apixaban ranks top among all the outcome indicators,which can be used as the preferred drug for VTE.More clinical studies are needed to determine whether NOACs have advantages over warfarin in terms of safety for severe bleeding and CRNM bleeding rates.

关 键 词：新型口服抗凝药 华法林 静脉血栓栓塞 网状Meta分析 随机对照试验 试验序贯分析 

分 类 号：R969.3[医药卫生—药理学]