Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin by 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, McLeod H L in Clinical pharmacology and therapeutics (2008). PubMed

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.

[ hide abstract ]

Discussed In Paper

Related In Paper

Variant Annotations

Sign in to see variant annotations.