A pharmacogenomic approach to coumarin anticoagulant therapy
Coordinator: Anke-Hilse MAITLAND-VAN DER ZEE
Project Number: 223062
EC contribution: € 2,544,891
The effectiveness of treatment with oral anticoagulants in the prevention of thrombotic disorders is well established, but these drugs are potentially dangerous because of their narrow therapeutic index. In Europe three coumarins are used: warfarin, acenocoumarol, and phenprocoumon. Genetic factors that have been recently demonstrated to change the pharmacokinetics and pharmacodynamics of coumarins are the presence of polymorphisms in the genes encoding for CYP2C9 and VKOR (vitamin K epoxide reductase complex). Polymorphisms in these genes are associated with increased risk for severe overanticoagulation and bleedings. A clinical trial will be performed in seven European countries to determine whether knowledge of the genotype of patients at the start of coumarin treatment will increase the safety of use of these compounds and whether such gene testing is cost-effective. Patients will be randomized to receive treatment with a coumarin either dosed with an algorithm that does not include information on their genotype, or with an algorithm that does contain this information. The primary outcome will be time within therapeutic INR range. Secondary outcomes include INR>4 and bleedings.