Role of pharmacogenomics in the management of traditional and novel oral anticoagulants

Larisa H. Cavallari*, Jaekyu Shin, Minoli A. Perera

*Corresponding author for this work

Research output: Contribution to journalReview article

39 Scopus citations

Abstract

Warfarin is the most commonly prescribed oral anticoagulant. However, it remains a difficult drug to manage mostly because of its narrow therapeutic index and wide interpatient variability in anticoagulant effects. Over the past decade, there has been substantial progress in our understanding of genetic contributions to variable warfarin response, particularly with regard to warfarin dose requirements. The genes encoding for cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are the major genetic determinants of warfarin pharmacokinetics and pharmacodynamics, respectively. Numerous studies have demonstrated significant contributions of these genes to warfarin dose requirements. The CYP2C9 gene has also been associated with bleeding risk with warfarin. The CYP4F2 gene influences vitamin K availability and makes minor contributions to warfarin dose requirements. Less is known about genes influencing warfarin response in African-American patients compared with other racial groups, but this is the focus of ongoing research. Several warfarin pharmacogenetic dosing algorithms and United States Food and Drug Administration-cleared genotyping tests are available for clinical use. Clinical trials are ongoing to determine the clinical utility and cost-effectiveness of genotype-guided warfarin dosing. Results from these trials will likely influence clinical uptake and third party payer reimbursement for genotype-guided warfarin therapy. There is still a lack of pharmacogenetic data for the newly approved oral anticoagulants, dabigatran and rivaroxaban, and with other oral anticoagulants in the research and development pipeline. These data, once known, could be of great importance as routine monitoring parameters for these agents are not available.

Original languageEnglish (US)
Pages (from-to)1192-1207
Number of pages16
JournalPharmacotherapy
Volume31
Issue number12
DOIs
StatePublished - Dec 2011

Keywords

  • CYP2C9 gene
  • Cytochrome P450
  • Dabigatran
  • Genotype
  • Pharmacogenetics
  • Polymorphism
  • VKORC1 gene
  • Vitamin K epoxide reductase complex subunit 1
  • Warfarin

ASJC Scopus subject areas

  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Role of pharmacogenomics in the management of traditional and novel oral anticoagulants'. Together they form a unique fingerprint.

  • Cite this