Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Int J Med Sci. 2012;9(6):472-9. doi: 10.7150/ijms.4637. Epub 2012 Aug 10.
The polymorphisms of VKORC1 and CYP2C9 play increasingly important roles in the inter-individual variability in warfarin dose. This study aimed to evaluate the feasibility of clinical application of pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality with rheumatic heart disease after valve replacement in a randomized and controlled trial.
One hundred and one consecutive patients of Han nationality with rheumatic heart disease undergoing valve surgery were enrolled and randomly assigned to an experimental group (n=50, based on CYP2C9 and VKORC1 genotypes, pharmacogenetic-based "predicted warfarin dose" for 3 days and then was adjusted to INR until stable warfarin maintenance dose) or a control group (n=51, 2.5mg/d for 3 days and then was adjusted to INR until stable warfarin maintenance dose). All included patients were followed for 50 days after initiation of warfarin therapy. The primary end-point was the time to reach a stable warfarin maintenance dose.
During the follow-up, 84.0% patients in the experimental group and 58.8% patients in the control group received warfarin maintenance dose. Compared with control group, patients in the experimental group had shorter mean time elapse from initiation of warfarin therapy until warfarin maintenance dose (27.5±1.8 d versus 34.7±1.8 d, p<0.001). Cox regression revealed that group (HR for experimental versus control group: 1.568, 95%CI 1.103-3.284) and age were two significant variables related to the time elapse from initiation of warfarin therapy until warfarin maintenance dose. The predicted warfarin maintenance dose was prominently correlated with the actual warfarin maintenance dose (r=0.684, p<0.001).
Based on CYP2C9 and VKORC1 genotypes, the pharmacogenetic-based warfarin-dosing algorithm may shorten the time elapse from initiation of warfarin therapy until warfarin maintenance dose. It is feasible for the clinical application of the pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality with rheumatic heart disease after valve replacement.
VKORC1 和 CYP2C9 的多态性在华法林剂量的个体间差异中起着越来越重要的作用。本研究旨在通过随机对照试验评估基于遗传药理学的华法林剂量算法在汉族风湿性心脏病瓣膜置换术后患者中的临床应用可行性。
连续纳入 101 例汉族风湿性心脏病患者，接受瓣膜手术，随机分为实验组（n=50，基于 CYP2C9 和 VKORC1 基因型，给予基于遗传药理学的“预测华法林剂量”3 天，然后调整 INR 至稳定的华法林维持剂量）或对照组（n=51，给予 2.5mg/d 3 天，然后调整 INR 至稳定的华法林维持剂量）。所有纳入患者在华法林治疗开始后随访 50 天。主要终点是达到稳定华法林维持剂量的时间。
在随访期间，实验组 84.0%的患者和对照组 58.8%的患者接受了华法林维持剂量。与对照组相比，实验组患者从开始华法林治疗到华法林维持剂量的平均时间更短（27.5±1.8d 与 34.7±1.8d，p<0.001）。Cox 回归显示，组（实验组与对照组的 HR：1.568，95%CI 1.103-3.284）和年龄是与从开始华法林治疗到华法林维持剂量的时间相关的两个显著变量。预测的华法林维持剂量与实际的华法林维持剂量显著相关（r=0.684，p<0.001）。
基于 CYP2C9 和 VKORC1 基因型，基于遗传药理学的华法林剂量算法可缩短从开始华法林治疗到华法林维持剂量的时间。基于遗传药理学的华法林剂量算法在汉族风湿性心脏病瓣膜置换术后患者中的临床应用是可行的。
