1. ¹Department of Internal Medicine, Section of Cardiology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
2. ²Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
3. ³Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan
4. ⁴Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
5. ⁵Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
6. ⁶Department of Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
7. ⁷Department of Cardiovascular Surgery, Chung-Ho Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
8. ⁸Department of Medicine, Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan
9. ⁹Department of Pharmacy, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
10. ¹⁰Department of Public Health, Chang Gung University College of Medicine, Taoyuan, Taiwan
11. ¹¹Chang Gung Institute of Technology, Taoyuan, Taiwan
12. ¹²Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA
13. ¹³These authors contributed equally to this work.

Correspondence: Y-T Chen, (chen0010@ibms.sinica.edu.tw)

Received 13 June 2007; Accepted 18 October 2007; Published online 9 January 2008.

Abstract

Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han-Chinese patients without prior warfarin treatments. Using the genotype-based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR >4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R² of 0.62). This study demonstrated that pharmacogenetics-based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.