Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-09

AUTHORS

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

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 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. More... »

PAGES

326-331

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/clpt.2008.10

DOI

http://dx.doi.org/10.1038/clpt.2008.10

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049494234

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18305455


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