Warfarin Pharmacogenetics: New Life for an Old Drug

Warfarin was first introduced in the 1950s and quickly became the most commonly used oral anticoagulant for the prevention of thromboembolism in patients with deep vein thrombosis, atrial fibrillation, or prosthetic heart valve replacement. Warfarin is highly effective in treating these diseases; however, several factors prevent it from even wider use, especially in Asian populations. It is difficult for patients on warfarin to reach desired anticoagulation due to its narrow therapeutic index and highly variable dose response. The major adverse event is bleeding which is associated with overdose of warfarin. Clinical and genetic factors such as polymorphisms in CYP2C9 and VKORC1 associated with an individual's warfarin maintenance have been identified. More than 20 dose prediction algorithms incorporating both genetic and clinical factors have been developed, and some of them have been tested clinically. However, most of the algorithms were tested in small populations. Several major clinical trials are now underway. This review aims to provide an overview of the field of warfarin which includes information about the drug, genetics of warfarin dose requirements, dosing algorithms developed and the challenges of clinical implementation of warfarin pharmacogenetics.