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. 2008 Sep;84(3):326-31.
doi: 10.1038/clpt.2008.10. Epub 2008 Feb 27.

Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin

B F Gage  1 , C Eby, J A Johnson, E Deych, M J Rieder, P M Ridker, P E Milligan, G Grice, P Lenzini, A E Rettie, C L Aquilante, L Grosso, S Marsh, T Langaee, L E Farnett, D Voora, D L Veenstra, R J Glynn, A Barrett, H L McLeod
Affiliations

Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin

B F Gage et al. Clin Pharmacol Ther. 2008 Sep.

Erratum in

  • Clin Pharmacol Ther. 2008 Sep;84(3):430

Abstract

Initiation of warfarin therapy using trial-and-error dosing is problematic. Our goal was to develop and validate a pharmacogenetic algorithm. In the derivation cohort of 1,015 participants, the independent predictors of therapeutic dose were: VKORC1 polymorphism -1639/3673 G>A (-28% per allele), body surface area (BSA) (+11% per 0.25 m(2)), CYP2C9(*)3 (-33% per allele), CYP2C9(*)2 (-19% per allele), age (-7% per decade), target international normalized ratio (INR) (+11% per 0.5 unit increase), amiodarone use (-22%), smoker status (+10%), race (-9%), and current thrombosis (+7%). This pharmacogenetic equation explained 53-54% of the variability in the warfarin dose in the derivation and validation (N= 292) cohorts. For comparison, a clinical equation explained only 17-22% of the dose variability (P < 0.001). In the validation cohort, we prospectively used the pharmacogenetic-dosing algorithm in patients initiating warfarin therapy, two of whom had a major hemorrhage. To facilitate use of these pharmacogenetic and clinical algorithms, we developed a nonprofit website, http://www.WarfarinDosing.org.

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Figures

Figure 1
Figure 1
Scatter plot showing the relationship between the pharmacogenetics-predicted dose (horizontal axis) and therapeutic dose (vertical axis) in the validation cohort.
See this image and copyright information in PMC

References

    1. Higashi MK, et al. Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA. 2002;287:1690–1698. - PubMed
    1. White RH, Beyth RJ, Zhou H, Romano PS. Major bleeding after hospitalization for deep-venous thrombosis. Am. J. Med. 1999;107:414–424. - PubMed
    1. Beyth RJ, Quinn L, Landefeld CS. A multicomponent intervention to prevent major bleeding complications in older patients receiving warfarin. A randomized, controlled trial. Ann. Intern. Med. 2000;133:687–695. - PubMed
    1. Hirsh J, Fuster V, Ansell J, Halperin JL. American heart association/American college of cardiology foundation guide to warfarin therapy. Circulation. 2003;107:1692–1711. - PubMed
    1. Ezekowitz MD, James KE, Radford MJ, Rickles FR, Redmond N. Initiating and maintaining patients on warfarin anticoagulation: the importance of monitoring. J. Cardiovasc. Pharmacol. Ther. 1999;4:3–8. - PubMed

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