Genetic data provided in real-time studied in blood-thinning therapy
ORLANDO, Nov. 7 – Genotype-guided dosing has the potential to reduce the risks associated with taking an important drug, warfarin, whose dose varies from person to person and must be tightly controlled. During the presentation of a late-breaking trial in this area at the American Heart Association’s Scientific Sessions 2007, researchers reported they have found they could get the genetic information they needed quickly and efficiently.
COUMA-GEN is the first randomized, controlled trial aimed at improving patient care by tapping genetic codes to predict the needed dose of the blood thinner in individuals, information that should improve its safety and efficacy.
“The idea behind this study is that the future of medicine needs to be more personal,” said Jeffrey Anderson, M.D., lead author of the study and professor of medicine at the University of Utah in Salt Lake City, Utah. “We can use genotyping to fine tune prescriptions based on detailed information about an individual and their metabolism, which will lead to fewer side effects.”
Thinning the blood with warfarin is a common yet potentially dangerous therapy for patients following orthopedic surgery or in other settings – but too high a dose causes excessive bleeding, too low a dose allows clots to form.
“Warfarin is ideal for testing because it has a very narrow therapeutic window,” Anderson said. That means that the effective dose can be only a little lower than a dose that could cause bleeding. And this is truer for patients with some genetic characteristics than for others. “Now we can genotype patients quickly by swabbing the inside of the cheek, putting the swab in a sort of test tube and checking their DNA for liver and metabolism issues that can affect the patient’s sensitivity to the drug,” he said.
The study involved 206 men and women who were 18 or older; of any ethnicity and with life expectancies greater than a year; were starting chronic outpatient warfarin therapy for atrial fibrillation; or had had emergency treatment of clotting of veins and pulmonary embolism; had been in the hospital for at least a month after orthopedic surgery; or had heart failure. Participants were randomized in a double-blind manner to a genotype-based warfarin dose initiation and maintenance algorithm or to a standard, empiric-dosing algorithm.
Participants were randomized in a double-blind manner to a genotype-based warfarin dose initiation and maintenance algorithm or to a standard, empiric-dosing algorithm.
“While we did identify the feasibility of prospective, randomized trials of PG-guided therapy and that genotyping in clinical “real-time” was possible, the primary endpoint of reduction in percent of patients whose INR (a measure of the effect of warfarin) were out-of-range was not achieved,” Anderson said. “These techniques still have promise, but we haven’t yet identified the precise setting or patient group where they will be the most helpful.”
Support for this study was provided by Deseret Foundation and the Heart and Lung Institute, LDS Hospital, Intermountain Healthcare, Salt Lake City, Utah and Critical-Path Institute, Tucson, Arizona.
Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.
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