title: Clinical application of pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality after rheumatic valve replacement: a randomized and controlled trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Xinhua Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
authors.forename: MingSong
authors.initials: M
authors.lastname: Wang
authors.forename: XiLong
authors.initials: X
authors.lastname: Lang
authors.forename: ShiTao
authors.initials: S
authors.lastname: Cui
authors.forename: Ke
authors.initials: K
authors.lastname: Fei
authors.forename: LiangJian
authors.initials: L
authors.lastname: Zou
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.forename: LiangXu
authors.initials: L
authors.lastname: Wang
authors.forename: ShengHui
authors.initials: S
authors.lastname: Zhang
authors.forename: XinTian
authors.initials: X
authors.lastname: Wu
authors.forename: YiLing
authors.initials: Y
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ji
mesh_terms: D000328:Adult; D000465:Algorithms; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods*; D012216:Rheumatic Diseases / Q000601:surgery*; D014859:Warfarin / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D014859:Warfarin