Genotype-based dosing algorithms for warfarin therapy: data review and recommendations.

Johnson EG, Horne BD, Carlquist JF, Anderson JL.

Source

Cardiovascular Department, Intermountain Medical Center, Salt Lake City, UT, USA.

Abstract

Warfarin, the most common oral anticoagulant, is the ideal candidate for pharmacogenetic dosing and gene-based 'individualization' of care. A plethora of studies have shown that stable dose requirements can be predicted using sequence variants in the CYP2C9 and VKORC1 genes in both sexes and in different races. Multiple clinical trials of pharmacogenetic warfarin dosing have been conducted with various methods, including several randomized trials that have been completed. These studies have reported varying degrees of success and some have been met with substantial skepticism. Other much larger randomized trials are ongoing. This paper reviews and synthesizes the various clinical trials that have been published and touches on the potential that the ongoing trials offer. The emergence of new oral anticoagulants also raises the question of the relevance of pharmacogenetic warfarin dosing for the future. The cost of genotype-guided dosing is substantial, and none of the studies to date have shown a cost-benefit of using pharmacogenetic warfarin dosing in clinical practice. Although pharmacogenetics-guided warfarin dosing has been discussed for many years, the currently available data regarding this genetically individualized dosing suggest that pharmacogenetics remains unproven for use in clinical warfarin prescription.