心房颤动患者使用新型口服抗凝药有效性和安全性的网状Meta分析
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摘要
背景心房颤动是临床上最常见的心律失常之一,血栓形成是心房颤动的常见并发症。长期以来华法林作为心房颤动患者抗凝的首选药物,其不良反应一直困扰着临床医生和患者。目前随着新型口服抗凝药的问世,这一难题得到了解决,相关的大型临床试验也验证了其疗效,但是仍然缺乏新型口服抗凝药之间直接的比较。目的采用网状Meta分析方法评价心房颤动患者使用新型口服抗凝药的治疗效果。方法计算机检索PubMed、EMBase、the Cochrane Library、Web of Science、中国生物医学文献数据库(CBM)、万方数据知识服务平台、中国知网(CNKI)等数据库,搜集关于新型口服抗凝药治疗心房颤动患者的随机对照试验(RCTs),检索截止时间为2018年7月。对纳入文献进行质量评价及数据提取,采用R 3.4.3和Stata 14软件对栓塞发生率、颅内出血发生率、缺血性脑卒中发生率、全因死亡率、心肌梗死发生率、胃肠道出血发生率等进行分析;采用曲线下面积(SUCAR)计算对干预措施进行排序。结果共纳入28篇RCTs,227 919例患者。网状Meta分析结果显示,使用华法林栓塞发生率高于达比加群150 mg、利伐沙班20 mg、阿哌沙班10 mg和依度沙班60 mg(P<0.05);使用华法林颅内出血发生率高于达比加群110 mg、达比加群150 mg、利伐沙班20 mg、阿哌沙班10 mg、依度沙班30 mg、依度沙班60 mg(P<0.05);使用华法林缺血性脑卒中发生率高于达比加群150 mg(P<0.05);除西美加群36 mg、利伐沙班15 mg外,使用华法林全因死亡率高于其他新型口服抗凝药(P<0.05);使用华法林心肌梗死发生率高于西美加群36 mg(P<0.05);使用华法林胃肠道出血发生率低于利伐沙班20 mg(P<0.05)。SUCAR对干预措施的排序结果显示,在降低栓塞发生率、全因死亡率方面,达比加群150 mg效果最好;在降低颅内出血、胃肠道出血发生率方面,依度沙班30 mg效果最好;在降低缺血性脑卒中、心肌梗死发生率方面,西美加群36 mg效果最好。结论现有的证据表明阿哌沙班10 mg可能是应用前景较好的药物。本研究纳入文献的总体质量较高,结果有一定的指导意义,但是纳入的国内文献质量不高,仍需要在国内开展更多高质量的临床试验对本研究的结果给予验证。
Background Atrial fibrillation(AF) is one of the most common arrhythmias encountered clinically.Thrombosis is a common complication of AF.For a long time,warfarin was a first choice for anticoagulation in patients with AF.But adverse reactions of warfarin have been troubled clinicians and patients.At present,with the new anticoagulants generated,and their efficacies have been verified by large-scale clinical trials,this problem has been solved.But there is still lack of direct comparative studies of such anticoagulants.Objective To evaluate the therapeutic effect of novel oral anticoagulants in patients with AF by network meta-analysis.Methods Databases of PubMed,EMBase,the Cochrane Library,Web of Science,CBM,Wanfang Data,CNKI were searched for randomized controlled trials(RCTs) concerning novel oral anticoagulants in patients with AF from inception to July,2018.Quality assessment and data extraction from the included RCTs were performed.Statistical analyses of the incidence of embolization,intracranial hemorrhage,ischemic stroke,myocardial infarction,and gastrointestinal bleeding,and all-cause mortality were conducted with R 3.4.3 and Stata 14 software.Surface under the cumulative ranking(SUCAR) was used to rank the value of the treatments.Results A total of 28 RCTs were included,involving 261 272 patients.The results of network meta-analysis showed that the incidence of embolic events associated with warfarin was higher than that caused by dabigatran(150 mg),rivaroxaban(20 mg),apixaban(10 mg),and edoxaban(60 mg)(P<0.05).The incidence of intracranial hemorrhage related with warfarin was higher than that caused by dabigatran(110 mg),dabigatran(150 mg),rivaroxaban(20 mg),apixaban(10 mg),edoxaban(30 mg)and edoxaban(60 mg)(P<0.05).Warfarin was associated with a higher incidence of ischemic stroke compared with dabigatran(150 mg)(P<0.05).Other treatments,except for ximelagatran(36 mg) and rivaroxaban(15 mg),were associated with lower all-cause mortality compared with warfarin(P<0.05).Warfarin was associated with a higher incidence of myocardial infarction compared with ximelagatran(36 mg)(P<0.05).But it was associated with a lower incidence of gastrointestinal bleeding compared with rivaroxaban(20 mg)(P<0.05).SUCAR values of all the interventions demonstrated that,dabigatran(150 mg) was associated with lower incidence of embolization and all-cause mortality;edoxaban(30 mg) was related to lower incidence of intracranial hemorrhage and gastrointestinal bleeding;ximelagatran(36 mg) was associated with lower incidence of ischemic stroke and myocardial infarction.Conclusion Available evidence shows that apixaban(10 mg) may be a promising treatment.The overall quality of the included studies is high,and the analysis results have certain guiding significance.However,considering the unsatisfied quality of the included domestic studies,our results need to be verified by more high-quality domestic studies.
Background Atrial fibrillation(AF) is one of the most common arrhythmias encountered clinically.Thrombosis is a common complication of AF.For a long time,warfarin was a first choice for anticoagulation in patients with AF.But adverse reactions of warfarin have been troubled clinicians and patients.At present,with the new anticoagulants generated,and their efficacies have been verified by large-scale clinical trials,this problem has been solved.But there is still lack of direct comparative studies of such anticoagulants.Objective To evaluate the therapeutic effect of novel oral anticoagulants in patients with AF by network meta-analysis.Methods Databases of PubMed,EMBase,the Cochrane Library,Web of Science,CBM,Wanfang Data,CNKI were searched for randomized controlled trials(RCTs) concerning novel oral anticoagulants in patients with AF from inception to July,2018.Quality assessment and data extraction from the included RCTs were performed.Statistical analyses of the incidence of embolization,intracranial hemorrhage,ischemic stroke,myocardial infarction,and gastrointestinal bleeding,and all-cause mortality were conducted with R 3.4.3 and Stata 14 software.Surface under the cumulative ranking(SUCAR) was used to rank the value of the treatments.Results A total of 28 RCTs were included,involving 261 272 patients.The results of network meta-analysis showed that the incidence of embolic events associated with warfarin was higher than that caused by dabigatran(150 mg),rivaroxaban(20 mg),apixaban(10 mg),and edoxaban(60 mg)(P<0.05).The incidence of intracranial hemorrhage related with warfarin was higher than that caused by dabigatran(110 mg),dabigatran(150 mg),rivaroxaban(20 mg),apixaban(10 mg),edoxaban(30 mg)and edoxaban(60 mg)(P<0.05).Warfarin was associated with a higher incidence of ischemic stroke compared with dabigatran(150 mg)(P<0.05).Other treatments,except for ximelagatran(36 mg) and rivaroxaban(15 mg),were associated with lower all-cause mortality compared with warfarin(P<0.05).Warfarin was associated with a higher incidence of myocardial infarction compared with ximelagatran(36 mg)(P<0.05).But it was associated with a lower incidence of gastrointestinal bleeding compared with rivaroxaban(20 mg)(P<0.05).SUCAR values of all the interventions demonstrated that,dabigatran(150 mg) was associated with lower incidence of embolization and all-cause mortality;edoxaban(30 mg) was related to lower incidence of intracranial hemorrhage and gastrointestinal bleeding;ximelagatran(36 mg) was associated with lower incidence of ischemic stroke and myocardial infarction.Conclusion Available evidence shows that apixaban(10 mg) may be a promising treatment.The overall quality of the included studies is high,and the analysis results have certain guiding significance.However,considering the unsatisfied quality of the included domestic studies,our results need to be verified by more high-quality domestic studies.
引文
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