Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin.

Published

Journal Article

Initiation of warfarin therapy using trial-and-error dosing is problematic. Our goal was to develop and validate a pharmacogenetic algorithm. In the derivation cohort of 1,015 participants, the independent predictors of therapeutic dose were: VKORC1 polymorphism -1639/3673 G>A (-28% per allele), body surface area (BSA) (+11% per 0.25 m(2)), CYP2C9(*)3 (-33% per allele), CYP2C9(*)2 (-19% per allele), age (-7% per decade), target international normalized ratio (INR) (+11% per 0.5 unit increase), amiodarone use (-22%), smoker status (+10%), race (-9%), and current thrombosis (+7%). This pharmacogenetic equation explained 53-54% of the variability in the warfarin dose in the derivation and validation (N= 292) cohorts. For comparison, a clinical equation explained only 17-22% of the dose variability (P < 0.001). In the validation cohort, we prospectively used the pharmacogenetic-dosing algorithm in patients initiating warfarin therapy, two of whom had a major hemorrhage. To facilitate use of these pharmacogenetic and clinical algorithms, we developed a nonprofit website, http://www.WarfarinDosing.org.

Full Text

Duke Authors

Cited Authors

  • Gage, BF; Eby, C; Johnson, JA; Deych, E; Rieder, MJ; Ridker, PM; Milligan, PE; Grice, G; Lenzini, P; Rettie, AE; Aquilante, CL; Grosso, L; Marsh, S; Langaee, T; Farnett, LE; Voora, D; Veenstra, DL; Glynn, RJ; Barrett, A; McLeod, HL

Published Date

  • September 2008

Published In

Volume / Issue

  • 84 / 3

Start / End Page

  • 326 - 331

PubMed ID

  • 18305455

Pubmed Central ID

  • 18305455

Electronic International Standard Serial Number (EISSN)

  • 1532-6535

Digital Object Identifier (DOI)

  • 10.1038/clpt.2008.10

Language

  • eng

Conference Location

  • United States