Genetic Test Predicts Response to Warfarin

By Ed Edelson
HealthDay Reporter
Wednesday, March 5, 2008; 6:00 PM

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WEDNESDAY, March 5 (HealthDay News) -- Variations of a gene that determines a person's sensitivity to warfarin are important in determining the initial doses of the anti-clotting drug, researchers report.

That information already is being put to medical use. Last August, the U.S. Food and Drug Administration changed the labeling to say that doctors should consider a genetic test when first prescribing warfarin, better known by its brand name, Coumadin.

"This test can save $1.1 billion in health-care costs and 18,000 lives a year," said Dr. Raymond Woosley, president of the Critical Path Institute, a private organization that is working with the FDA and the biotechnology industry on the subject.

The FDA estimates that 2 million Americans take warfarin to prevent potentially dangerous blood clots. Reasons range from implantation of an artificial heart valve to the abnormal heartbeat called atrial fibrillation.

But warfarin is a notoriously difficult drug to manage, especially at the start. Too much can lead to hemorrhages; too little can allow clots to form. One individual may do well on 1.5 milligrams a day, while another may require 20 milligrams daily.

Some medical centers run elaborate tests to determine the starting dose, but "the standard way is to start with 5 milligrams, then titrate the doses according to blood tests that show the response to warfarin," said Dr. C. Michael Stein, a professor of medicine and pharmacology at Vanderbilt University. He was the leader of the group reporting the finding in the March 6 issue of the New England Journal of Medicine.

Two genes are known to affect the response to warfarin. One, designated CYP2C9, governs the metabolism of the medication, or how fast it is eliminated from the body. The other, designated VKORC1, governs sensitivity, or how the body reacts to a given dose of warfarin. The new study of 297 people starting warfarin therapy showed that variants of the sensitivity gene should be considered in the first prescription, Stein said.