Influence ofCYP2C9andVKORC1on warfarin dose, anticoagulation attainment and maintenance among European–Americans and African–Americans

Abstract

Aims: The influence of CYP2C9 and VKORC1 on warfarin dose, time to target International Normalized Ratio (INR), time to stabilization, and risk of over-anticoagulation (INR: >4) was assessed after adjustment for clinical factors, intraindividual variation in environmental factors and unobserved heterogeneity. Materials & Methods: Common CYP2C9 and VKORC1 polymorphisms were assessed in 302 European–Americans and 273 African–Americans receiving warfarin. Race-stratified multivariable analyses evaluated the influence of CYP2C9 and VKORC1 on warfarin response. Results & Conclusion:CYP2C9 and VKORC1 accounted for up to 30% of the variability in warfarin dose among European–Americans and 10% among African–Americans. Neither CYP2C9 nor VKORC1 influenced the time to target INR or stabilization among patients of either race, and neither influenced the risk of over-anticoagulation among African–Americans. The risk of over-anticoagulation was higher among European–Americans with variant VKORC1 1173C/T (p < 0.01) and marginally significant among those with variant CYP2C9 (p = 0.08) genotype. Although CYP2C9 and VKORC1 genotyping can facilitate individualized initiation of warfarin dose in African and European–Americans, the ability to predict the risk of over-anticoagulation is inconsistent across race. Identification of other factors that can predict such risk consistently in a racially diverse group will facilitate individualized maintenance of warfarin therapy.