Validation of warfarin pharmacogenetic algorithms in clinical practice

Pharmacogenomics. 2012 Jan;13(1):21-9. doi: 10.2217/pgs.11.120.


Aim: 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.

Patients & 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / genetics
  • Clinical Medicine
  • Cohort Studies
  • Cytochrome P-450 CYP2C9
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Heart Diseases / drug therapy*
  • Heart Diseases / genetics
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / genetics*
  • Pharmacogenetics
  • Vitamin K Epoxide Reductases
  • Warfarin / administration & dosage
  • Warfarin / therapeutic use*


  • Warfarin
  • Mixed Function Oxygenases
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases