Point: Use of Pharmacogenetics in Guiding Treatment with Warfarin

Abstract

Warfarin is the most widely used oral anticoagulant for the treatment of thromboembolic disorders and for stroke prophylaxis. Warfarin is a problematic drug because it exhibits large interindividual variation in the required therapeutic dose, has a narrow therapeutic range, and shows multiple food and drug interactions. Its anticoagulant effect is monitored by measuring the international normalized ratio (INR), which is a function of the time required for a patient’s blood to coagulate relative to the time it takes for a reference blood sample. Although warfarin has been used in humans for more than 50 years, its main side effect—bleeding—is a leading cause of hospital admission and drug-related death(1)(2). This problem has made patients and clinicians yearn for a new efficient and safe oral anticoagulant drug that does not require frequent monitoring. In Europe, a new oral anticoagulant drug (dabigatran) claimed to have these qualities has been licensed for short-term primary prevention of venous thromboembolic events, but its effectiveness in long-term secondary thromboprophylaxis remains to be shown. Furthermore, the daily cost of dabigatran is 5 times that of warfarin therapy including INR tests. To switch all warfarin patients (currently 1% of the population in many Western countries) to dabigatran would boost national costs in countries with subsidized drug programs; therefore, national authorities will probably encourage the continued use of warfarin, even when oral thrombin inhibitors become available for long-term thromboprophylaxis. Given that warfarin …