Development of a pharmacogenetic-based warfarin dosing algorithm and its performance in Brazilian patients: highlighting the importance of population-specific calibration

Author:

Santos Paulo Caleb Junior Lima1,Marcatto Leiliane Rodrigues1,Duarte Nubia Esteban1,Gadi Soares Renata Alonso1,Cassaro Strunz Celia Maria2,Scanavacca Maurício3,Krieger Jose Eduardo1,Pereira Alexandre Costa

Affiliation:

1. Laboratory 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

2. Clinical Laboratory, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil

3. Clinical Cardiology Division, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil

Abstract

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

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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