Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin
Document Type
Article
Publication Title
Clinical Pharmacology and Therapeutics
Abstract
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 m2), 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. © 2008 American Society for Clinical Pharmacology and Therapeutics.
First Page
326
Last Page
331
DOI
10.1038/clpt.2008.10
Publication Date
1-1-2008
Recommended Citation
Gage, B. F.; Eby, C.; Johnson, J. A.; Deych, E.; Rieder, M. J.; Ridker, P. M.; Milligan, P. E.; Grice, G.; Lenzini, P.; Rettie, A. E.; Aquilante, C. L.; Grosso, L.; Marsh, S.; Langaee, T.; Farnett, L. E.; Voora, D.; Veenstra, D. L.; Glynn, R. J.; Barrett, A.; and McLeod, H. L., "Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin" (2008). Pharmacy Practice Faculty Publications. 627.
https://doi.org/10.1038/clpt.2008.10
https://collections.uhsp.edu/pharm-practice_pubs/627