title: Current challenges in personalizing warfarin therapy.
abstract: In an exciting era where novel oral anticoagulants, such as the factor Xa and direct thrombin inhibitors, are beginning to emerge as therapeutic options, the vitamin K antagonists (VKAs) such as warfarin, which have been in clinical use for over half a century, will remain an important part of the therapeutic landscape for the foreseeable future. The optimal effectiveness and safety of the VKAs is limited by significant inter- and intra- patient variability in dose response. As such, routine laboratory monitoring with subsequent dose adjustment to achieve and maintain an international normalized ratio (INR) that falls within a narrow therapeutic range is necessary; even with frequent INR monitoring, time in therapeutic range of VKAs is generally <60% in usual care settings. Yet, personalized approaches to warfarin therapy, such as the routine incorporation of pharmacogenetic data into dose selection and adjustment, the selective use of prescribed doses of vitamin K for those patients with unstable INRs, and integration of patient self-testing /self-management, has the potential to improve the safety, efficacy and ease of use of warfarin. To date, no randomized trials have proven the benefits of routine pharmacogenetic testing for warfarin initiation; however, pivotal trials are ongoing. Through further investigative work, allowing these personalized strategies to realize their full potential, warfarin may remain a preferred therapeutic oral anticoagulant for years to come.
authors: Department of Pathology, University of Utah, ARUP Laboratories, UT, USA.
authors: Gwendolyn A
authors: GA
authors: McMillin
authors: Sara R
authors: SR
authors: Vazquez
authors: Robert C
authors: RC
authors: Pendleton
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods / Q000639:trends; D057285:Precision Medicine / Q000379:methods* / Q000639:trends; D014812:Vitamin K / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage* / Q000097:blood
chemical_list: D014812:Vitamin K; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases