Evaluation of Pharmacogenetic Algorithm for Warfarin Dose Requirements in Japanese Patients

• Published in: Circulation Journal Vol. 74; no. 5; pp. 977 - 982
• Main Authors: Takeuchi, Fumihiko, Hiroe, Michiaki, Kashida, Mitsuo, Kashima, Toshitaka, Fukuda, Shoji, Tanaka, Yuriko, Hosaka, Shigeru, Kimura, Sosuke, Kato, Norihiro, Okazaki, Osamu
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 2010
• Subjects: Aged; Alcohol Drinking; Algorithms; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Anticoagulation; Aryl Hydrocarbon Hydroxylases - genetics; Asian Continental Ancestry Group; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - ethnology; Cardiovascular Diseases - genetics; Cohort Studies; CYP2C9; Cytochrome P-450 CYP2C9; Female; Genotype; Humans; International Normalized Ratio; Japan; Male; Middle Aged; Mixed Function Oxygenases - genetics; Pharmacogenetics; Pharmacogenetics - methods; Polymorphism, Genetic; Smoking; Vitamin K Epoxide Reductases; VKORC1; Warfarin; Warfarin - administration & dosage; Warfarin - adverse effects
• ISSN: 1346-9843; 1347-4820; 1347-4820
• DOI: 10.1253/circj.CJ-09-0876

Background: Warfarin dosing is difficult to establish because of considerable interindividual variation. Thus, warfarin pharmacogenetics have attracted particular interest in relation to appropriate control of anticoagulation. Methods and Results: The 200 eligible subjects were chosen from participants in a hospital cohort. Performance of a pharmacogenetic algorithm recently developed by the International Warfarin Pharmacogenetics Consortium (IWPC) was tested and compared with a clinical algorithm (without genotype data) by calculating the percentage of patients for whom the predicted dose deviated by less than 7 mg/week (1 mg/day) from the actual dose. The pharmacogenetic algorithm accurately identified a significantly (P<0.05) larger proportion of patients to achieve the target international normalized ratio than did the clinical algorithm (68% vs 36% for a low-dose group; and 21% vs 0% for a high-dose group). Also, an increase in warfarin dosage was found to be appropriate for the current status of alcohol drinking (4 mg/week, as against non-drinking) and smoking (3.3 mg/week, as against non-smoking). Conclusions: The IWPC pharmacogenetic algorithm has clinical application, particularly in identifying Japanese patients who require a low dosage of warfarin and are at greater risk of excessive anticoagulation. (Circ J 2010; 74: 977 - 982)