Key result
A pharmacogenetic-driven warfarin-dosing algorithm combining CYP2C9 and VKORC1 genotypes with clinical factors explained >66% of dose variance in Puerto Rican patients, outperforming prior models.
Why the study?
Does a population-specific pharmacogenetic-guided dosing algorithm improve ideal warfarin dose estimates in Puerto Rican patients compared to previously published models?
Observational (n=218)
Yes
Does a population-specific pharmacogenetic-guided dosing algorithm improve ideal warfarin dose estimates in Puerto Rican patients compared to previously published models?
A population-specific pharmacogenetic algorithm incorporating CYP2C9 and VKORC1 genotypes significantly improves warfarin dose prediction in Puerto Rican patients compared to standard models.
Supports genotype-guided dosing estimates in Puerto Ricans; extends prior models yet leaves open need for prospective validation.
AIM: This study was aimed at developing a pharmacogenetic-driven warfarin-dosing algorithm in 163 admixed Puerto Rican patients on stable warfarin therapy. PATIENTS & METHODS: A multiple linear-regression analysis was performed using log-transformed effective warfarin dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other relevant nongenetic clinical and demographic factors as independent predictors. RESULTS: The model explained more than two-thirds of the observed variance in the warfarin dose among Puerto Ricans, and also produced significantly better 'ideal dose' estimates than two pharmacogenetic models and clinical algorithms published previously, with the greatest benefit seen in patients ultimately requiring <7 mg/day. We also assessed the clinical validity of the model using an independent validation cohort of 55 Puerto Rican patients from Hartford, CT, USA (R(2) = 51%). CONCLUSION: Our findings provide the basis for planning prospective pharmacogenetic studies to demonstrate the clinical utility of genotyping warfarin-treated Puerto Rican patients.
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Ramos et al. (2012) conducted an observational in Stable warfarin therapy (n=218). Pharmacogenetic-guided warfarin dosing algorithm vs. Previously published pharmacogenetic models and clinical algorithms was evaluated on Log-transformed effective warfarin dose. A pharmacogenetic-driven warfarin-dosing algorithm combining CYP2C9 and VKORC1 genotypes with clinical factors explained >66% of dose variance in Puerto Rican patients, outperforming prior models.
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