Simvastatin use reduced warfarin dose requirements by 29% in carriers of the CYP2C9*3 allele compared with 5% in noncarriers, indicating a genetic predisposition to this drug interaction.
Observational (n=1,132)
Does the CYP2C9*3 polymorphism influence the drug-drug interaction between warfarin and simvastatin?
The CYP2C9*3 polymorphism significantly increases the magnitude of the drug-drug interaction between warfarin and simvastatin, leading to a greater reduction in warfarin dose requirements.
Absolute Event Rate: 29% vs 5%
BACKGROUND: Simvastatin interacts with warfarin, but the strength of the interaction varies between individual patients, indicating a genetic predisposition. PATIENTS & METHODS: The influence of the CYP2C9*2 and CYP2C9*3 polymorphisms on the interaction between simvastatin and warfarin was analyzed in data from 1132 patients. RESULTS: Simvastatin use reduced warfarin dose requirements by 29% in carriers of the CYP2C9*3 allele, compared with 5% in noncarriers. A regression model showed a significant influence of CYP2C9*3 on the drug-drug interaction, predicting a warfarin dose reduction of 25% in CYP2C9*3 heterozygotes and 43% in CYP2C9*3 homozygotes. CONCLUSION: Our data indicate that the CYP2C9*3 polymorphism predisposes for a pharmacologic interaction between warfarin and simvastatin.
Andersson et al. (Tue,) conducted a observational in Patients taking warfarin and simvastatin (n=1,132). Simvastatin use in carriers of CYP2C9*3 allele vs. Simvastatin use in noncarriers was evaluated on Reduction in warfarin dose requirements. Simvastatin use reduced warfarin dose requirements by 29% in carriers of the CYP2C9*3 allele compared with 5% in noncarriers, indicating a genetic predisposition to this drug interaction.