Warfarin Pharmacogenetics: Ready for Clinical Utility?

Linnea M. Baudhuin

doi:10.29074/ascls.22.3.151

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Linnea M. Baudhuin, PhD, DABMG⇑
1. is assistant professor, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN

Address for correspondence: Linnea M. Baudhuin, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, (507) 284-2511, (507) 266 4176 (fax). baudhuin.linnea{at}mayo.edu

Extract

Despite the Federal Drug Administration's August 2007 relabeling of warfarin to recommend pharmacogenetic (PGx) testing, the clinical application remains controversial. Many questions exist regarding how information gleaned from genetic testing can be applied in warfarin therapy. In particular, does PGx testing lead to a shorter time to stable INR compared to prudent international normalized ratio (INR) monitoring coupled with the consideration of age, BMI, diet, and physical condition? Does it reduce clinical complications? Other topics of uncertainty include whether the correct warfarin dose can be obtained based on genotype, whether PGx testing is cost-effective, and turn-around-time. Despite the reservations about warfarin PGx testing, there are several subsets of patients for whom such testing could be beneficial.

BACKGROUND Warfarin sodium is a commonly prescribed anticoagulant used for the prevention of thromboembolic events and treatment of thromboembolic disorders. The annual number of outpatient warfarin prescriptions increased by 45% from 1998 to 2004 in the U.S., from 21.1 million to 30.6 million ¹. With the aging population and projected increased prevalence of atrial fibrillation, the number of warfarin prescriptions is predicted to continue to increase^1,2.

There are many challenges in regulating warfarin dosing. Warfarin has a very narrow therapeutic window and when the prothrombin time or INR falls outside of target range, there is an increased risk for major bleeding or thrombotic complications. Typically, the INR during warfarin treatment should optimally fall between two and three for most patients, although the target INR may vary depending on indication for treatment^3,4. A large study…

ABBREVIATIONS: CYP2C9 = cytochrome P450 2C9; INR= international normalized ratio; PGx = pharmacogenetic; VKOR = vitamin K epoxide reductase; VKORC1 = vitamin K epoxide reductase, complex 1; AERS = Adverse Event Reporting System