Optimisation of warfarin-dosing algorithms for Han Chinese patients with CYP2C9*13 variants.

BACKGROUND

Existing pharmacogenetic algorithms cannot fully explain warfarin dose variability in all patients. CYP2C913 is an important allelic variant in the Han Chinese population. However, adjustment of warfarin dosing in CYP2C913 variant carriers remains unclear. To the best of our knowledge, this study is the first to assess the effects of adjusting warfarin dosages in Han Chinese patients harbouring CYP2C9*13 variants.

METHODS

In total, 971 warfarin-treated Han Chinese patients with atrial fibrillation were enrolled in this study. Clinical data were collected, and CYP2C9*2, 3, 13 and VKORC1-1639 G > A variants were genotyped. We quantitatively analysed the effect of CYP2C913 on warfarin maintenance dose and provided multiplicative adjustments for CYP2C913 using validated pharmacogenetic algorithms.

RESULTS

Approximately 0.6% of the Han Chinese population carried CYP2C913 variant, and the genotype frequency was between those of CYP2C92 and CYP2C93. The warfarin maintenance doses were significantly reduced in CYP2C913 carriers. When CYP2C913 variants were not considered, the pharmacogenetic algorithms overestimated warfarin maintenance doses by 1.03-1.16 mg/d on average. The actual warfarin dose in CYP2C913 variant carriers was approximately 40% lower than the algorithm-predicted dose. Adjusting the warfarin-dosing algorithm according to the CYP2C9*13 allele could reduce the dose prediction error.

CONCLUSION

Our study showed that the algorithm-predicted doses should be lowered for CYP2C913 carriers. Inclusion of the CYP2C913 variant in the warfarin-dosing algorithm tends to predict the warfarin maintenance dose more accurately and improves the efficacy and safety of warfarin administration in Han Chinese patients.