Pharmacogenetics of coumarin anticoagulant therapy

Coumarins are effective drugs for treatment and prevention of thromboembolic events. However, their use requires a balancing act between the chance of underdosing which increases the risk of thromboembolic events and the chance of overdosing which increases the risk of haemorrhages. It has been shown that polymorphisms in VKORC1 and CYP2C9 explain 35-50% of the dose variability, although patient characteristics and environmental factors also play a role. In this book chapter we discuss the pharmacogenetics of coumarin derivatives, clinical trials investigating the effectiveness of pre-treatment genotyping and the cost-effectiveness of pharmacogenetic-guided dosing