Warfarin Pharmacogenetics

Abstract

SummaryThere has been significant interest in the pharmacogenetics of warfarin therapy with the recent package insert update highlighting its potential role in improving the safety and effectiveness of warfarin. Herein we review the evidence of the influence of the two key genes of interest, CYP2C9 and VKORC1, on warfarin response, and discuss the implications of current knowledge for clinical practice.The influence of CYP2C9 and VKORC1 genotype on warfarin dose requirements has been consistently demonstrated in diverse racial/ ethnic patient groups in observational studies and randomized clinical trails. Dosing algorithms have been developed that incorporate clinical, demographic, and genetic information to help select a starting warfarin dose. Furthermore, CYP2C9 variant genotypes have been associated with a significantly increased risk of serious bleeding events.However evidence to date from prospective, controlled studies has not demonstrated an added benefit of incorporating genotype-guided therapy in improving anticoagulation control, preventing or reducing the risk of hemorrhagic or thromboembolic complications. Research efforts designed to evaluate the effectiveness of genotype-guided therapy in improving outcomes are underway. However the routine use of CYP2C9 and VKORC1 genotyping in the general patient population initiating warfarin therapy is not supported by evidence currently available.