Variations of a gene that determines a person's sensitivity to warfarin (Coumadin), an anti-clotting drug, are important in determining the initial doses of the medication, researchers report.
That information already is being put to medical use. The US Food and Drug Administration (FDA) changed the drug's labeling to say that doctors should consider a genetic test when first prescribing warfarin. "This test can save $1.1 billion in health care costs and 18,000 lives a year," said Raymond Woosley, MD, PhD, president of the Critical Path Institute, a private organization that is working with the FDA and the biotechnology industry on the subject.
Background
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, and too little can allow clots to form. One individual may do well on 15 milligrams (mg) a day, while another may require 20 mg 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 C. Michael Stein, MD, a professor of medicine and pharmacology at Vanderbilt University and leader of the study group.
The Study
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 VKORCI, 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, Dr. Stein said.
Tailoring Treatment To Genetic Makeup
Dr. Stein is a leader in the new field of pharmacogenomics (the study of how genes affect a person's response to drugs), which hopes to tailor medical treatment to each individual's genetic makeup. The field has been made possible by the Human Genome Project, which has mapped the full human genetic makeup. That information has led the US government to sponsor programs on specific applications of pharmacogenomics and to a small but growing industry of companies developing and marketing genetic tests, such as one for warfarin sensitivity.
Several warfarin sensitivity tests are now available, costing perhaps $500 or $600, Dr. Woosley said.
Implications
"This is not something that changes the way doctors practice tomorrow," Dr. Stein said of the new study. "It is additional information on the relative importance of these two genes early in therapy which will refine the way that physicians use warfarin."
And the tests are useful only when warfarin treatment starts, Dr. Woosley said. They do not eliminate the need for periodic blood tests to make precise adjustments to warfarin dosage.
Nevertheless, said Dina Paltoo, PhD, MPH, the National Heart, Lung, and Blood Institute program director who oversaw the agency's funding of the study, "this can help physicians clarify what dose a patient should get, so it could reduce adverse drug effects, toxicity and bleeding."
Testing should be done because “these genetic variations are critically important in how warfarin affects each individual,” Dr. Paltoo said.
