CYP2C9和VKORC1基因检测指导华法林给药的有效性和安全性的Meta分析(英文)  

Efficacy and safety of CYP2C9 and VKORC1 genotype testing for dosing of warfarin: a meta- analysis

作　　者：史长城[1] 田港[2] 吴静 楼江[1] 严伟[1] 

机构地区：[1]杭州市第一人民医院药学部,浙江杭州310006 [2]浙江中医药大学,浙江杭州310053 [3]杭州市妇产科医院药剂科,浙江杭州310008

出　　处：《中国新药与临床杂志》2015年第11期850-857,共8页Chinese Journal of New Drugs and Clinical Remedies

基　　金：Hospital pharmacy special research funded projects of Zhejiang Pharmaceutical Association(2014ZYY18)

摘　　要：目的综合评价CYP2C9和VKORC1基因检测指导华法林给药的有效性和安全性。方法采用Meta分析方法,制定原始文献的纳入标准、排除标准及检索策略,检索Pubmed、Embase、Cochrane图书馆、中国期刊全文数据库、维普数据库和万方数据库,采用Revman 5.2软件对满足纳入标准的RCTs研究进行Meta分析。主要观察指标为国际标准化比率(INR)治疗窗内时间、出血发生率,次要观察指标为INR大于4发生率和华法林剂量调整次数。结果共检索出973篇文献,符合纳入标准的8篇随机对照研究,共计2 347例患者。Meta分析结果显示CYP2C9和VKORC1基因导向的华法林给药模式可以显著降低出血事件发生率[RR=0.83,95%CI(0.70,0.98),P=0.03],减少华法林剂量调整次数[MD=-0.55,95%CI(-0.93,-0.16),P=0.005]。尽管在INR治疗窗内时间[MD=2.16,95%CI(-2.36,6.68),P=0.35]、INR大于4发生率[RR=0.90,95%CI(0.71,1.15),P=0.40]两个方面,CYP2C9和VKORC1基因导向的华法林给药模式与传统给药模式无显著差异,但是基因导向的华法林给药模式仍有增加INR治疗窗内时间,减少INR大于4发生率的趋势。结论 CYP2C9和VKORC1基因检测指导华法林给药可以提高华法林给药的安全性和有效性。AIM To evaluate the efficacy and safety of CYP2C9 and VKORC1 genotype testing for dosing of warfarin. METHODS Using meta-analysis method, randomized controlled trials （RCTs） evaluating efficacy and safety of CYP2C9 and VKORC 1 genotype testing for dosing of warfarin published on or before June 2014 were searched in PubMed, Embase, Cochrane Library, CNKI, Chinese VIP database and Chinese Wanfang database. The methodological qualities of RCTs were assessed according to the Cochrane Collaboration. Meta- analysis was performed using Revman 5.2 software. The primary outcomes included time within the therapeutic range and bleeding events. Secondary outcomes included frequency of international normalized ratio （INR） 〉 4 and dose adjustments per patient. RESULTS Nine hundred and seventy-three potentially relevant articles were searched and eight studies involving 2 347 patients were included in the meta-analysis. Genotype- guided approach appeared to significantly lower the risk of bleeding events （RR = 0.83, 95%CI （0.70, 0.98）, P = 0.03） and dose adjustments （MD = -0.55, 95%CI （-0.93, -0.16）, P = 0.005）. There were a trend towards increasing the percentage of time within the therapeutic range （MD = 2.16, 95% CI （-2.36, 6.68）, P = 0.35） and lowering frequency of INR 〉 4 （RR = 0.90, 95%CI （0.71, 1.15）, P = 0.40） in genotype-guided group, although meta-analysis didn＇t show significant difference. CONCLUSION CYP2C9 and VKORC1 genotype testing may improve the safety and efficacy in the initial stage of warfarin dosing.

关 键 词：华法林 遗传药理学 治疗结果 安全 META分析 

分 类 号：R973.2[医药卫生—药品]