华法林稳定剂量预测算法的临床应用

目的 探讨针对中国人群的基于遗传因素的华法林稳定剂量预测算法临床应用的可行性.方法 2008年8月至2009年9月,贵州省人民医院心外科收集126例拟行心脏瓣膜置换术患者的临床资料及血样,采用PCR结合熔解曲线分析方法对维生素K环氧化物还原酶复合体1( VKORC1)和细胞色素P450 (CYP)2 C9两个基因进行分型.受试者计算机随机分为试验组(n=59)和对照组(n=56),试验组患者的前3次用药按预测剂量服用,对照组患者初始剂量为2.5 mg/d,两组患者均根据国际标准化比值(INR)的变化逐步调整至稳定剂量,并随访50 d.结果 50 d随访结束时,试验组和对照组分别有82.4％ (42/51)和62.5％(30/48)的患者获得稳定剂量.试验组和对照组患者获得稳定剂量的平均时间分别是(27.5±1.8)和(34.7±1.8)d,中位时间分别是(24.0±1.7)和(33.0 ±4.5)d,两组患者获得稳定剂量的时间差异有统计学意义(P=0.012).试验组与对照组患者获得稳定剂量时间比较的风险比(HR)为1.786(95％CI1.088～2.875,P=0.026).结论 结合遗传因素和非遗传因素的华法林稳定剂量预测算法可显著缩短患者华法林稳定剂量的调整时间,经前瞻性研究证实其具有临床应用的可行性.

Clinical applications of dosing algorithm in the predication of warfarin maintenance dose

Objective To evaluate the feasibility of clinical application for genetic based dosing algorithm in the predication of warfarin maintenance dose in Chinese population.Methods The clinical data were collected and blood samples harvested from a total of 126 patients undergoing heart valve replacement.The genotypes of VKORC1 and CYP2C9 were determined by melting curve analysis after PCR.They were divided randomly into the study and control groups.In the study group,the first three doses of warfarin were prescribed according to the predicted warfarin maintenance dose while warfarin was initiated at 2.5 mg/d in the control group.The warfarin doses were adjusted according to the measured international normalized ratio (INR) values.And all subjects were followed for 50 days after an initiation of warfarin therapy.Results At the end of a 50-day follow-up period,the proportions of the patients on a stable dose were 82.4％ (42/51)and 62.5％ (30/48) for the study and control groups respectively.The mean durations of reaching a stable dose of warfarin were (27.5 ± 1.8) and ( 34.7 ± 1.8 ) days and the median durations were ( 24.0 ± 1.7 ) and (33.0±4.5)days in the study and control groups respectively. Significant differences existed in the durations of reaching a stable dose between the two groups (P =0.012).Compared with the control group,the hazard ratio (HR) for the duration of reaching a stable dose was 1.786 in the study group (95％ CI 1.088 - 2.875,P =0.026).Conclusion The predicted dosing algorithm incorporating genetic and nongenetic factors may shorten the duration of achieving efficiently a stable dose of warfarin.And the present study validates the feasibility of its clinical application.