Warfarin pharmacogenomics: current best evidence

Abstract

The utility of using genetic information to guide warfarin dosing has remained unclear based on prior observational studies and small clinical trials. Two larger trials of warfarin and one of the acenocoumarol and phenprocoumon have recently been published. The COAG trial addressed the incremental benefit of adding genetic information to clinical information and demonstrated no benefit from the pharmacogenetic-based dosing strategy on the primary outcome. The EU-PACT UK trial compared an algorithm approach using genetic and clinical information to one that used a relatively fixed starting dose. The pharmacogenetic-based algorithms improved the primary outcome. The study of acenocoumarol and phenprocoumon compared a pharmacogenetic with a clinical algorithm and demonstrated no benefit on the primary outcome. The evidence to date does not support an incremental benefit of adding genetic information to clinical information on anticoagulation control. However, compared with fixed dosing, a pharmacogenetic algorithm can improve anticoagulation control.

Keywords: drug therapy; genetics; pharmacogenetics; randomized controlled trials as topic; warfarin.