Key result
An admixture-adjusted pharmacogenetic algorithm predicted the ideal warfarin dose in 45.5% of high-risk Caribbean Hispanic patients compared to 29% using a clinical non-genetic algorithm.
Why the study?
Does an admixture-adjusted, genotype-guided pharmacogenetic algorithm improve the predictability of effective warfarin dosing compared to clinical non-genetic algorithms in Caribbean Hispanics?
Observational (n=310)
Open-label
Yes
Does an admixture-adjusted, genotype-guided pharmacogenetic algorithm improve the predictability of effective warfarin dosing compared to clinical non-genetic algorithms in Caribbean Hispanics?
Absolute Event Rate: 45.5% vs 29%
p-value: p=<0.001
Incorporating genetic admixture and specific genotypes into warfarin dosing algorithms significantly improves dose prediction accuracy in Caribbean Hispanic patients compared to standard clinical algorithms.
May improve warfarin dose prediction in Caribbean Hispanics; leaves open need for outcome trials before adoption.
AIM: This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients. PATIENTS & METHODS: A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals. RESULTS: The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R2 = 0.70, MAE = 0.72mg/day) than a clinical algorithm that excluded genotypes and admixture (R2 = 0.60, MAE = 0.99mg/day), and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p<0.001). The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias). CONCLUSIONS: Results supported our rationale to incorporate individual's genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics. TRIAL REGISTRATION: ClinicalTrials.gov NCT01318057.
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Duconge et al. (2016) conducted an observational in Thromboembolic disorders requiring warfarin therapy (n=310). Admixture-adjusted pharmacogenetic warfarin dosing algorithm vs. Clinical non-genetic algorithm was evaluated on Ideal dose prediction (within 20% of actual dose) in patients at highest risk of adverse events (p=<0.001). An admixture-adjusted pharmacogenetic algorithm predicted the ideal warfarin dose in 45.5% of high-risk Caribbean Hispanic patients compared to 29% using a clinical non-genetic algorithm.
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