达比加群酯抗凝治疗安全性的系统评价

Systematic evaluation on the safety of dabigatran for anticoagulant therapy

目的系统评价达比加群酯抗凝治疗的安全性。方法检索PubMed、ClinicalTrials.gov、中国知网等数据库中关于达比加群酯治疗各类栓塞疾病的随机对照研究,截至2015年6月。用Stata 13.1及Rev Man 5.3软件进行Meta分析。结果共纳入16项随机对照研究,总计42395例患者。达比加群酯相比对照药可显著降低严重出血发生率(P<0.05),尤其是与华法林相比结果显著(P<0.01),但随剂量增加,达比加群酯严重出血发生率呈现增高趋势。达比加群酯可显著增加心肌梗死发生率(P<0.01),其中与华法林比较结果显著(P<0.01),且达比加群酯心肌梗死发生率与剂量呈正相关。达比加群酯可显著增加消化道出血发生率(P<0.01),与华法林或安慰剂相比结果更为显著(P<0.05),且达比加群酯消化道出血发生率与剂量呈正相关。漏斗图检测不存在发表偏倚,敏感性分析证实结果可靠。结论达比加群酯可引起心肌梗死和消化道出血风险高,临床使用中需充分权衡利弊。

Objective To evaluate the safety of dabigatran etexilate in the anticoagulant therapy.Methods The randomized controlled trials about dabigatran etexilate in the treatment of all kinds of embolism diseases,which had been published from the time of library foundation to June,2015 were collected from PubMed,ClinicalTrials.gov,CNKI database according to the following criterias.An the same time results of studies were analyzed through using Stata 13.1 software and Rev Man5.3 software.Results Sixteen randomized controlled trials were included,involving 42395 patients.Meta- analysis showed that dabigatran etexilate could significantly reduce the incidence of major bleeding comparing with comparators（P0.05）,especially compared with warfarin（P〈0.01）.However the incidence of major bleeding with dabigatran etexilate was similar to comparators when the dosage was increased.Moreover dabigatran etexilate could significantly increase the risk of myocardial infarction（P〈0.01）,especially compared with warfarin（P〈0.01）.while the incidence of myocardial infarction with dabigatran etexilate was increased with the increase of the dosage.In addition dabigatran etexilate could significantly increase the incidence of gastrointestinal bleeding（P〈0.01）,especially compared with warfarin and placebo（P〈0.05）,which was dose- dependent.There was no publication bias in funnel plots and sensitivity analysis indicated the results were reliable.Conclusion The use of dabigatran etexilate was associated with a significant increase in the risk of myocardial infarction and gastrointestinal bleeding.Therefore,clinicians need to take these risks into account in treatment.