Genetic Testing for Warfarin Therapy Initiation

• Published in: The Annals of pharmacotherapy Vol. 42; no. 9; pp. 1298 - 1303
• Main Authors: Hynicka, Lauren M, Cahoon, William D, Jr, Bukaveckas, Bonny L
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA Harvey Whitney Books 01-09-2008; SAGE Publications; Whitney
• Subjects: Anticoagulants - adverse effects; Biological and medical sciences; Genetic Predisposition to Disease; Hemorrhage - chemically induced; Hemorrhage - genetics; Humans; Medical sciences; Pharmacology. Drug treatments; Warfarin - adverse effects; VKORC1; CYP2C9; pharmacogenomics; pharmacogenetics; anticoagulation; warfarin; Human; Pharmacogenetics; Warfarin; Enzyme; Isozyme; Coumarine derivatives; Cytochrome P450; Genomics; VKORC1 gene; Anticoagulant; Predictive medicine; Antivitamin K; Treatment; Vitamin-K-epoxide reductase (warfarin-sensitive); Genetics; Oxidoreductases; Initiation; CYP2C9 gene; Pharmacogenomics
• ISSN: 1060-0280; 1542-6270
• DOI: 10.1345/aph.1L127

Objective
To review the literature regarding the efficacy of genetic testing for determining the appropriate initial dose of warfarin and the effect that this testing has on the safety and efficacy of therapy.
Data Sources:
Searches of MEDLINE (1966–May 2008) and Cochrane Database (1993–May 2008) were conducted using the search terms warfarin, anticoagulation, pharmacogenomics, pharmacogenetics, CYP2C9, VKORC1, and interindividual variability. Limits included articles written in English with human subjects. Additional data were identified through bibliographic reviews.
Study Selection And Data Extraction:
All English-language articles identified from the data sources were evaluated. Studies were eligible for inclusion if they evaluated the efficacy of pharmacogenomic testing to improve outcomes with initiation of warfarin therapy.
Data Synthesis:
The use of warfarin presents numerous challenges in clinical practice. Four studies (N = 38, 48, 200, 297) evaluating the efficacy of genetic testing for determining the initial dose of warfarin therapy have been published. Results show that time to therapeutic international normalized ratio (INR) and time to stable warfarin dose are similar regardless of genotype. When conventional warfarin dosing was compared with pharmacogenomic-based dosing, no significant difference was seen between groups in terms of time spent within the target INR range (41.5% vs 41.7%; no p value reported). Similar results were found in a subsequent study in which patients receiving conventional dosing were outside their target INR range 33.1% of the time compared with 30.7% of the lime for patients whose dose was guided by pharmacogenomics (p = 0.47).
Conclusions:
There is growing evidence that variant alleles for CYP2C9 and VKORC1 genotypes account for a proportion of the variability seen in warfarin dosing. The currently available literature related to the use of pharmacogenomic testing in the initiation of warfarin therapy does not show improved outcomes in either safety or efficacy with warfarin therapy and therefore does not support the routine use of pharmacogenomic testing when initiating warfarin therapy.