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Development and comparison of warfarin dosing algorithms for stroke patients

 Sun-Mi Cho  ;  Kyung-Yul Lee  ;  Jong Rak Choi  ;  Kyung-A Lee 
 Yonsei Medical Journal, Vol.57(3) : 635-640, 2016 
Journal Title
 Yonsei Medical Journal 
Issue Date
Aged ; Algorithms* ; Anticoagulants/administration & dosage* ; Anticoagulants/therapeutic use ; Cytochrome P-450 CYP2C9/genetics* ; Dose-Response Relationship, Drug ; Female ; Genotype ; Humans ; International Normalized Ratio ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Pharmacogenetics ; Regression Analysis ; Republic of Korea ; Stroke/drug therapy* ; Stroke/ethnology ; Vitamin K Epoxide Reductases/genetics* ; Warfarin/administration & dosage* ; Warfarin/therapeutic use
CYP2C9 ; Korean ; VKOC1 ; stroke ; warfarin
PURPOSE: The genes for cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) have been identified as important genetic determinants of warfarin dosing and have been studied. We developed warfarin algorithm for Korean patients with stroke and compared the accuracy of warfarin dose prediction algorithms based on the pharmacogenetics. MATERIALS AND METHODS: A total of 101 patients on stable maintenance dose of warfarin were enrolled. Warfarin dosing algorithm was developed using multiple linear regression analysis. The performance of all the algorithms was characterized with coefficient of determination, determined by linear regression, and the mean of percent deviation was used to predict doses from the actual dose. In addition, we compared the performance of the algorithms using percentage of predicted dose falling within ±20% of clinically observed doses and dividing the patients into a low-dose group (≤3 mg/day), an intermediate-dose group (3-7 mg/day), and high-dose group (≥7 mg/day). RESULTS: A new developed algorithms including the variables of age, body weight, and CYP2C9 and VKORC1 genotype. Our algorithm accounted for 51% of variation in the warfarin stable dose, and performed best in predicting dose within 20% of actual dose and intermediate-dose group. CONCLUSION: Our warfarin dosing algorithm may be useful for Korean patients with stroke. Further studies to elucidate clinical utility of genotype-guided dosing and find the additional genetic association are necessary.
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
이경아(Lee, Kyung A) ORCID logo https://orcid.org/0000-0001-5320-6705
이경열(Lee, Kyung Yul) ORCID logo https://orcid.org/0000-0001-5585-7739
조선미(Cho, Sun Mi)
최종락(Choi, Jong Rak) ORCID logo https://orcid.org/0000-0002-0608-2989
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