Abstract T P339: Pharmacogenetics Guided Algorithm Including Factors of Renal Impairment and Vitamin K Intake for Accurate Predicting of Individual Warfarin Dose in a Genetically Homogeneous Population
Warfarin is an efficacious anticoagulant because it can be tailored for therapy using PT-INR. However, highly variable interindividual dosing requirement becomes a problem in empirical dosing or dosing using only clinical characteristics. Thus, several pharmacogenetics-guided algorithms (PGAs) have been proposed.
We aimed to establish a PGA including factors of renal impairment and vitamin K (VK) intake and to evaluate its efficacy for more accurately predicting individual warfarin dose in genetically homogeneous population.
We studied a single-center prospective cohort study of 176 Japanese patients on stable, therapeutic doses of warfarin to establish a PGA in which VK intake and renal impairment were considered to predict individual maintenance dose. We used another data set of 157 Japanese patients obtained from a multicenter prospective cohort study and compared our results with the results of 2 previously proposed PGAs applied to the same database; one, from the International Warfarin Pharmacogenetic Consortium (IWPC) (N Engl J Med, 2009), which considered race (but not renal function or VK intake), and the other reported by Limdi et al. (Am J Kidney Dis, 2010), which considered renal function (but not race or VK intake).
Genotyping results showed that 80% patients had the homozygotes of CYP2C9 wild-type allele and VKORC1 -1639A variant, indicating the high genetic homogeneity in Japanese population. The mean observed maintenance doses (3.17 ± 1.09 mg/day) was compatible with that estimated by our algorithm (O: 3.13 ± 0.97) but was higher or lower than that by IWPC (I: 2.65 ± 0.71) or Limdi (L: 5.36 ± 0.92), respectively, although all algorithms showed similar coefficients of determination (O: 0.62, I: 0.67, L: 0.61). Our algorithm also revealed excellent results compared with others in terms of mean absolute error (O: 0.67 ± 0.63 mg/day, I: 0.75 ± 0.60, L: 2.19 ± 0.88) and the percent of patients whose doses were estimated within ±1.0 mg/day of the observed maintenance dose (O: 77.5%, I: 73.3%, L: 9.0%).Race seemed to be one of the most critical factors for PGA, and PGA including VK intake and renal impairment as factors appeared to be more accurate to predict individual warfarin dose in a genetically homogenous population such as Asians.
Author Disclosures: T. Tanaka: None. S. Miyata: Honoraria; Modest; Daiich-Sankyo Co.,Ltd.. A. Kada: None. H. Yamamoto: None. T. Miyata: Research Grant; Significant; Taisho Pharmaceutical Co., Ltd.. Honoraria; Modest; Alexion, Sysmex, Bayer, Daiichi-Sankyo, Mitsubishi Chemical Medience. K. Nagatsuka: Honoraria; Modest; Sanofi.
- © 2014 by American Heart Association, Inc.