Individualizing warfarin therapy

Abstract

Warfarin is the most commonly prescribed oral anticoagulant for the treatment and prevention of thromboembolic events. The correct maintenance dose of warfarin for a given patient is difficult to predict, the drug carries a high risk of toxicity, and variability among patients means that the safe dose range differs widely between individuals. Recent pharmacogenetic studies indicate that the routine incorporation of genetic testing into warfarin therapy protocols could substantially ease both the financial and health risks currently associated with this treatment. In particular, the variability in warfarin dose requirement is now recognized to be due, in large part, to polymorphisms in two genes: cytochrome P450 2C9 and the vitamin K epoxide reductase complex subunit 1. The development of algorithms that integrate all of the relevant genetic and physical factors into comprehensive, individualized predictive models for warfarin dose could be used to translate the results of pharmacogenetic testing into actionable clinical application.

Keywords: adverse drug reaction; anticoagulation; cytochrome P450 2C9; personalized medicine; pharmacogenetics; vitamin K epoxide reductase; warfarin; warfarin dosing.