Estimation of the Warfarin Dose with Clinical and Pharmacogenetic Data

• Published in: The New England journal of medicine Vol. 360; no. 8; pp. 753 - 764
• Main Authors: Klein, T E, Altman, R B, Eriksson, N, Gage, B F, Kimmel, S E, Lee, M-T M, Limdi, N A, Page, D, Roden, D M, Wagner, M J, Caldwell, M D, Johnson, J A
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 19.02.2009
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Anticoagulants - administration & dosage; Aryl Hydrocarbon Hydroxylases - genetics; Biological and medical sciences; Child; Clinical pharmacology; Cohort Studies; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug dosages; Drug therapy; Farmakologisk forskning; Female; Fysiologi och farmakologi; General aspects; Genotype; Humans; International Normalized Ratio; Klinisk farmakologi; Least-Squares Analysis; Male; Medical sciences; MEDICIN; MEDICINE; Middle Aged; Mixed Function Oxygenases - genetics; Pharmacogenetics; Pharmacological research; Physiology and pharmacology; Polymorphism, Single Nucleotide; Variables; Vitamin K Epoxide Reductases; Warfarin - administration & dosage; Young Adult; Medical data; Medicine; Antivitamin K; Pharmacogenetics; Warfarin; Coumarine derivatives; Estimation; Genetics; Anticoagulant; Dose
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa0809329

There is substantial variation in the dose of warfarin required to achieve therapeutic anticoagulation. In this study, mathematical models for warfarin dosage were constructed that used either clinical factors alone or clinical and genetic factors. The model incorporating genetic factors, when tested retrospectively with data from an international cohort, provided better estimates than a model that included only clinical factors. Mathematical models for warfarin dosage were constructed that used either clinical factors alone or clinical and genetic factors. The model incorporating genetic factors provided better estimates than a model that included only clinical factors. Warfarin is the most widely used oral anticoagulant agent worldwide; more than 30 million prescriptions were written for this drug in the United States in 2004. 1 The appropriate dose of warfarin is difficult to establish because it can vary by a factor of 10 among patients, and the consequences of taking an incorrect dose can be catastrophic. Because incorrect doses contribute to a high rate of adverse effects, there is interest in developing improved strategies for determining the appropriate dose. 2 Clinical factors, demographic variables, and variations in two genes — cytochrome P450, family 2, subfamily C, polypeptide 9 ( CYP2C9 . . .