Gene Test Improves Use of Coumadin (warfarin) for Stroke Prevention in Atrial Fibrillation

March 17, 2010 6:04 AM CT

By Peggy Noonan

New research shows a simple genetic test can help people with atrial fibrillation (AF) get the right dose of anticoagulant medicine. Approximately 2 million people take Coumadin®, or the generic version warfarin, to prevent blood clots.

According to the Medco-Mayo Warfarin Effectiveness Study presented this week at the American College of Cardiology’s 59th annual scientific session in Atlanta, Georgia, genetic testing to find the best blood thinner dose is especially important during start-up, when a person begins taking warfarin.

Anticoagulant drugs like warfarin are prescribed to people with AF to prevent dangerous blood clots that could cause stroke or other damage. The trick is to take enough to prevent clots without taking too much, which could cause bleeding or bruising.

But there’s no one-size-fits-all dosage recommendation. Factors such as health issues, age, medicines, supplements, foods, and alcohol consumption can affect blood thinning. That’s why doctors order frequent INR (International Normalized Ratio) or ProTime (prothrombin time) tests that measure coagulation rate, the speed at which blood clots.

Before this genetic sensitivity test, the only way to get the right starter dose of warfarin was by trial and error—take the medicine, take an INR test to check blood coagulation, adjust the dose, retest, and repeat.

“There have been no studies that demonstrate its [genetic testing] use in clinical practice,” says Thomas Moyer, Ph.D., from the Mayo Clinic’s Department of Laboratory Medicine and Pathology.  “All of the studies have been basic science showing the effect but nobody’s demonstrated that it makes a difference in a patient.”

The Medco-Mayo team studied 896 people from 49 states, all of whom were members of a Medco Health Solutions prescription benefit plan and had just started taking blood thinner prescriptions.

Genetic tests were done on samples collected from a cheek swab or blood. The researchers looked for two genes (CYP2C9 and VKO4C1) that determine genetic sensitivity to warfarin. They provided that genetic information to the doctors who were treating those 896 people, along with an explanation of how to interpret it. 

For example, if a person’s genetic test showed “high sensitivity to warfarin,” his or her doctor would be advised to reduce the dose and monitor blood tests more often. For “low sensitivity,” the doctor would be advised to increase the warfarin dose. 

How did it work?

The study showed that compared to a control group of people who took warfarin but didn’t have the genetic test, those who were tested for genetic sensitivity to warfarin were 31% less likely to be hospitalized for any reason during the first six months of blood thinner therapy and 29% less likely to be hospitalized for bleeding or clots. However, one criticism of the study when it was presented at ACC was the lack of INR data on participants.

“Genetic testing is a tool clinicians can use to more accurately predict the best warfarin dose early on,” says Robert S. Epstein, MD, chief medical officer and president of the Medco Research Institute in Franklin Lakes, New Jersey. Although the test may cost from about $250 to $400, he adds: “If we reduce just two hospitalizations per 100 patients tested, that more than compensates for the cost of genotyping.”

To learn more, see:

  • PT and INR: The Test — a primer from about tests used to monitor blood thinners

Peggy Noonan specializes in writing about health for consumers and medical professionals. She writes for leading national magazines and consumer publications as well as