Ann Lab Med.  2020 May;40(3):216-223. 10.3343/alm.2020.40.3.216.

Development and Validation of a Novel Warfarin Dosing Algorithm for Korean Patients With VKORC1 1173C

• Cho EH
• Lee K
• Yang M
• Choi R
• Baek SY
• Sohn I
• Kim JS
• On YK
• Bang OY
• Cho HJ
• Lee SY

• KMID: 2466014
• DOI: http://doi.org/10.3343/alm.2020.40.3.216

Abstract

BACKGROUND
Differences in the performance of suggested warfarin dosing algorithms among different ethnicities and genotypes have been reported; this necessitates the development of an algorithm with enhanced performance for specific population groups. Previous warfarin dosing algorithms underestimated warfarin doses in VKORC1 1173C carriers. We aimed to develop and validate a new warfarin dosing algorithm for Korean patients with VKORC1 1173C.
METHODS
A total of 109 patients carrying VKORC1 1173CT (N=105) or 1173CC (N=4) were included in this study. Multiple regression analysis was performed to deduce a new dosing algorithm. Following literature searches for genotype-guided warfarin dosing algorithms, 21 algorithms were selected and evaluated using the correlation coefficient (ρ) of actual dose and estimated dose, mean error, and root mean square error.
RESULTS
The developed algorithm is as follows: maintenance dose (mg/week)=exp [3.223−0.009×(age)+0.577×(body surface area [BSA])+0.178×(sex)−0.481×(CYP2C9 genotype)+0.227×(VKORC1 genotype)]. Integrated variables explained 44% of the variance in the maintenance dose. The predicted and actual doses showed moderate correlation (ρ=0.641) with the best performance with a mean error of −1.30 mg/week. The proportion of underestimated groups was 17%, which was lower than with the other algorithms.
CONCLUSIONS
This is the first study to develop and validate a warfarin dosing algorithm based on data from VKORC1 1173C carriers; it showed superior predictive performance compared with previously published algorithms.

Keyword

Warfarin; Genotype; VKORC1; Korea; Performance; Dosing algorithm

MeSH Terms

Genotype
Humans
Korea
Population Groups
Warfarin*
Warfarin

Figure

• 

  Fig. 1 Scatter plot showing Spearman correlation between actual and predicted warfarin doses using the leave-one-out cross validation (LOOCV) method (ρ=0.664, 95% CI: 0.543−0.757). The solid line is the regression line, and the dotted line is the 95% confidence interval.

• 

  Fig. 2 Percentages of patients with underestimated (green), ideal (blue), and overestimated (red) doses of warfarin among VKORC1 1173C carriers.

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