Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans

• Published in: Clinical pharmacology and therapeutics Vol. 84; no. 3; p. 332
• Main Authors: Schelleman, H, Chen, J, Chen, Z, Christie, J, Newcomb, C W, Brensinger, C M, Price, M, Whitehead, A S, Kealey, C, Thorn, C F, Samaha, F F, Kimmel, S E
• Format: Journal Article
• Language: English
• Published: United States 01.09.2008
• Subjects: African Americans; Algorithms; Anticoagulants - administration & dosage; Anticoagulants - therapeutic use; Aryl Hydrocarbon Hydroxylases - genetics; Cytochrome P-450 CYP2C9; Drug Labeling; European Continental Ancestry Group; Female; Humans; International Normalized Ratio; Linear Models; Male; Middle Aged; Mixed Function Oxygenases - genetics; Polymorphism, Genetic; Predictive Value of Tests; Thromboembolism - drug therapy; Vitamin K Epoxide Reductases; Warfarin - administration & dosage; Warfarin - therapeutic use
• ISSN: 1532-6535
• DOI: 10.1038/clpt.2008.101

The objective of this study was to determine whether warfarin dosing algorithms developed for Caucasians and African Americans on the basis of clinical, environmental, and genetic factors will perform better than an empirical starting dose of 5 mg/day. From April 2002 through December 2005, 259 subjects (Caucasians and African Americans) who started using warfarin were prospectively followed until they reached maintenance dose. The Caucasian algorithm included 11 variables (R(2) = 0.43). This model (which predicted 51% of the doses to within 1 mg of the observed dose) performed better than 5 mg/day (which predicted 29% of the doses to within 5 +/- 1 mg). The African-American algorithm included 10 variables (R(2) = 0.28). This model predicted 37% of the doses to within 1 mg of the observed dose, representing a small improvement compared with 5 mg/day (which predicted 34% of the doses to within 1 mg of 5 mg/day). These results were similar to the results we obtained from testing other published algorithms. The dosing algorithms explained <45% of the observed variability in Caucasians, and the algorithms performed only marginally better for African Americans when compared with giving 5 mg empirically.