Pharmacogenetics of coumarin anticoagulants in Brazilians

Abstract

Introduction: Coumarin vitamin K antagonists are the mainstay of anticoagulant therapy in atrial fibrillation, prosthetic heart valves and thromboembolic conditions. Concerns with these drugs include large inter-individual variability in dose requirements, narrow therapeutic index and need to monitor prothrombin time repeatedly.Areas covered: Pharmacogenetic studies and dosing algorithms for warfarin and phenprocoumon.Expert opinion: Gene candidate studies in Brazilian patients verified consistently the association of warfarin and pheprocoumon stable dose requirements with CYP2C9 and VKORC1 polymorphisms, and minor or no influence of other pharmacogenes (e.g., CYP4F2 and F7). The predictive power of warfarin and phenprocoumon dosing algorithms developed for Brazilians compares favorably with those reported for other populations. A warfarin dosing algorithm derived for an admixed cohort performed equally well in self-reported White and Black patients, in marked contrast with the considerably poorer performance of other warfarin algorithms in patients of African descent compared to those of European ancestry. This discrepancy is ascribed to the extensive European/African admixture among Brazilians. Prospective studies of clinical utility of coumarin dosing algorithms, in the context of the Brazilian Public Health System, would represent an important counterpart to recently published trials in European and North American cohorts with predominant or exclusive European ancestry.