Washington DC, March 30, 2009 - In the April issue of Clinical Chemistry, a series of articles looks at the emergence of personalized medicine and pharmacogenetic testing for guiding warfarin therapy. The issue at hand is whether new genetic-based tests offer clinically useful information that augments the traditional testing and biometric data used to determine drug dosing and efficacy in patients.
Warfarin is the most widely prescribed oral anticoagulant for treatment of clotting disorders and stroke prevention. Unfortunately, warfarin dosing is a challenge for physicians because individuals can have extensively different responses to a given dose of the drug. In addition, even though warfarin has been used clinically for over 50 years, its main side effect—bleeding—is a leading cause of hospital admission and drug-related mortality.
The first two Clin Chem articles examine new pharmacogenetic tests that analyze polymorphisms known to affect warfarin metabolism. One of these papers, from a multinational group of researchers, notes that “Pre-screening patients for [relevant] genotypes prior to prescription of the drug will facilitate a more rapid individualized determination of the proper maintenance dose for a patient, minimizing risk for adverse reaction and reoccurrence of thromboembolic episodes.” The second article, from scientists at Memorial Sloan Kettering Cancer Center in New York, describes a promising method for identifying genetic variations that are known to contribute to impaired warfarin metabolism. Study authors say that this information can be combined with other clinical parameters to improve warfarin dosing.
Another two articles offer a point/counterpoint of using pharmacogenetics for guiding warfarin treatment. The ‘pro’ side is laid out by Mia Wadelius, MD, from the University Hospital in Uppsala, Sweden, who points out that advanced testing methods are a worthwhile pursuit because of the expense of new anticoagulants that don’t need to be monitored. The ‘con’ side is taken by Charles Eby, MD, PhD, of Barnes Jewish Hospital in St. Louis, Mo. According to Eby, “Warfarin…is an ideal drug for applying the principles of pharmacogenetics,” but he points to a lack of large-scale studies and clinical trials to justify moving the new test technologies into clinical practice.”
In an important step toward this goal, NIH is launching a prospective, multi-center, randomized clinical trial in the United States to test whether a gene-based strategy for prescribing initial warfarin dose will improve patient outcomes. The trial began last month and will enroll 1,200 participants of diverse backgrounds and ethnicities at twelve clinical sites.
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