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Association of Apolipoprotein E Genotype with Duration of Time to Achieve a Stable Warfarin Dose in African-American Patients

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Title: Association of Apolipoprotein E Genotype with Duration of Time to Achieve a Stable Warfarin Dose in African-American Patients
Author(s): Cavallari, L.H.; Butler, C.; Langaee, T.Y.; Wardak, N.; Patel, S.R.; Viana, M.A.G.; Shapiro, N.L.; Nutescu, E.A.
Subject(s): warfarin genotype African American apolipoprotein E vitamin K
Abstract: Study Objective. To test the hypothesis that genotypes for proteins affecting vitamin K availability influence the duration of time required to achieve a stable warfarin dose in African-American patients. Design. Retrospective cohort study Setting. Pharmacist-managed antithrombosis clinic. Patients. Ninety-two African-American adults whose warfarin therapy was initiated between September 2, 1999, and July 8, 2009. Measurements and Main Results, During a routine anticoagulation clinic visit, a sample was collected from each patient for genetic analysis. Genotyping was performed for the following variants: apolipoprotein E epsilon 2, epsilon 3, and epsilon 4; NAD(P)H:quinone oxidoreductase (NQO1)*2; cytochrome P450 (CYP) 4F2 V433M; CYP2C9*2, *3, *5, *8, and *11; and vitamin K epoxide reductase complex 1 (VKORC1) -1639G>A. Patients' medical records were then reviewed, and data were collected retrospectively for each anticoagulation clinic visit during the first 6 months of warfarin therapy or until dose stabilization. The median time required to reach a stable warfarin dose, defined as the dose that produced therapeutic anticoagulation for three consecutive clinic visits, was 83 days. Compared with the 46 patients who achieved a stable warfarin dose within 83 days, the 46 patients who required longer durations for dose stabilization had a higher frequency of the apolipoprotein E epsilon 3/epsilon 3 genotype (37% vs 59%, p=0.037). Sixty-one percent of patients with the epsilon 3/epsilon 3 genotype versus 40% of those with an epsilon 2 or epsilon 4 allele had a delay in achieving a stable dose (p=0.037). Neither the CYP4F2 nor NQO1 genotype was associated with warfarin dose stabilization. Conclusion. Our data support the hypothesis that the apolipoprotein E genotype is associated with duration of time to reach a stable warfarin dose in African-American patients. Further insight into the genetic effects on warfarin dose stabilization could reveal novel methods to improve anticoagulation control during the warfarin initiation period.
Issue Date: 2011-08
Publisher: IOS Press
Citation Info: Cavallari, L. H., Butler, C., Langaee, T. Y., Wardak, N., Patel, S. R., Viana, M. A. G., Shapiro, N. L., & Nutescu, E. A. 2011. Association of Apolipoprotein E Genotype with Duration of Time to Achieve a Stable Warfarin Dose in African-American Patients. Pharmacotherapy, 31(8): 785-792. DOI: 10.1592/phco.31.8.785
Type: Article
Description: © 2011 by IOS Press, Pharmacotherapy Post print version of article may differ from published version. The definitive version is available through IOS Press at DOI:10.1592/phco.31.8.785
ISSN: 0277-0008
Sponsor: This study was supported by an American Foundation for Pharmaceutical Education New Investigator Award and a University of Illinois Hans Vahlteich Pharmacy Endowment Award to L.H.C.
Date Available in INDIGO: 2012-08-21

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