Huang Sheng-wen, Xiang Dao-kang, An Bang-quan, Li Gui-fang, Huang Ling, Wu Hai-li
Department of Laboratory Medicine, Guizhou Provincial People's Hospital, Guiyang, China.
Zhonghua Yi Xue Za Zhi. 2011 Dec 27;91(48):3421-5.
To evaluate the feasibility of clinical application for genetic based dosing algorithm in the predication of warfarin maintenance dose in Chinese population.
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.
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).
The predicted dosing algorithm incorporating genetic and non-genetic factors may shorten the duration of achieving efficiently a stable dose of warfarin. And the present study validates the feasibility of its clinical application.
评估基于基因的给药算法在中国人群中预测华法林维持剂量的临床应用可行性。
收集126例行心脏瓣膜置换术患者的临床资料并采集血样。采用聚合酶链反应（PCR）后熔解曲线分析测定维生素K环氧化物还原酶复合体亚单位1（VKORC1）和细胞色素P450 2C9（CYP2C9）的基因型。将患者随机分为研究组和对照组。研究组前三剂华法林根据预测的华法林维持剂量给药，而对照组华法林起始剂量为2.5mg/d。根据测得的国际标准化比值（INR）值调整华法林剂量。所有受试者在华法林治疗开始后随访50天。
在50天的随访期结束时，研究组和对照组达到稳定剂量的患者比例分别为82.4%（42/51）和62.5%（30/48）。研究组和对照组达到华法林稳定剂量的平均时间分别为（27.5±1.8）天和（34.7±1.8）天，中位时间分别为（24.0±1.7）天和（33.0±4.5）天。两组达到稳定剂量的时间存在显著差异（P=0.012）。与对照组相比，研究组达到稳定剂量时间的风险比（HR）为1.786（95%可信区间1.088 - 2.875，P=0.026）。
结合基因和非基因因素的预测给药算法可能缩短有效达到华法林稳定剂量的时间。本研究验证了其临床应用的可行性。
