title: Validation of warfarin pharmacogenetic algorithms in clinical practice.
abstract: OBJECTIVE
  The goal of this study was to evaluate the performance of four warfarin pharmacogenetic algorithms in a real clinical setting, namely the algorithms of Gage et al., Michaud et al., Wadelius et al. and the International Warfarin Pharmacogenetics Consortium algorithm.
  
  
  METHODS
  Data was obtained retrospectively for 605 patients who had initiated warfarin therapy at the Montreal Heart Institute. Warfarin dosing and International Normalized Ratio history were obtained from hospital charts and CYP2C9 and VKORC1 polymorphisms were genotyped.
  
  
  RESULTS
  The four algorithms produced similar accuracy with mean absolute error ranging from 1.36-1.52 mg/day and adjusted R(2) from 40-44%. Gage's algorithm and Wadelius' algorithm predicted the largest proportion of patients within ± 20% of their observed stable warfarin dose. For patients requiring low doses, Gage's algorithm provided the highest proportion of patients within ideal dose range (36.3%), while Wadelius' algorithm performed the best for patients requiring high doses (37.3% of patients within ideal dose range).
  
  
  CONCLUSIONS
  Our study demonstrates the value of published pharmacogenetic dosing algorithms for the prediction of warfarin doses, in particular for patients with low or high therapeutic dose requirements.
authors.affiliation: Faculté de Pharmacie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Mélina
authors.initials: M
authors.lastname: Marin-Leblanc
authors.forename: Sylvie
authors.initials: S
authors.lastname: Perreault
authors.forename: Imen
authors.initials: I
authors.lastname: Bahroun
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lapointe
authors.forename: Ian
authors.initials: I
authors.lastname: Mongrain
authors.forename: Sylvie
authors.initials: S
authors.lastname: Provost
authors.forename: Jacques
authors.initials: J
authors.lastname: Turgeon
authors.forename: Mario
authors.initials: M
authors.lastname: Talajic
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
authors.forename: Michael
authors.initials: M
authors.lastname: Phillips
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dubé
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000235:genetics; D015510:Clinical Medicine; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006331:Heart Diseases / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010597:Pharmacogenetics; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases