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Development of a pharmacogenetic-based warfarin dosing algorithm and its performance in Brazilian patients:
Paulo Caleb Junior Lima Santos1, Leiliane Rodrigues Marcatto1, Nubia Esteban Duarte1
1Laboratory of Genetics & Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44 Cerqueira Cesar, São Paulo, CEP 05403-000, Brazil.
Background:
The main aims of the present study were to develop a pharmacogenetic-based warfarin dosing algorithm and to validate it in a highly admixed population.
Materials & Methods:
We included two patient cohorts treated with warfarin (first cohort, n = 832; and second cohort, n = 133).
Results:
Our algorithm achieved a determination coefficient of 40% including the variables age, gender, weight, height, self-declared race, amiodarone use, enzyme inducers use, VKORC1 genotypes and predicted phenotypes according to CYP2C9 polymorphisms.
Conclusion:
Data suggest that our developed algorithm is more accurate than the IWPC algorithm when the application is focused on patients from the Brazilian population. Population-specific derivation and/or calibration of warfarin dosing algorithms may lead to improved performance compared with general use dosing algorithms currently available. Original submitted 26 November 2014; Revision submitted 9 April 2015.
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