Genetics May Help Fine-Tune Warfarin Dosage

ByABC News
February 18, 2009, 8:25 PM

Feb. 19 -- WEDNESDAY, Feb. 18 (HealthDay News) -- A DNA test could make prescribing the widely used anticoagulant warfarin safer by predicting the lowest effective dose, a new study finds.

The U.S. Food and Drug Administration estimates that 2 million Americans take warfarin to prevent potentially dangerous blood clots that can cause strokes. Reasons range from implantation of an artificial heart valve to the abnormal heartbeat called atrial fibrillation. But establishing and maintaining the ideal dose is done by trial and error, with weekly and monthly monitoring.

"In a very large group of patients, we showed that the use of genetics helps predict the right dose, and this may take the dangerous guesswork out of prescribing warfarin," said study co-author Dr. Russ Altman, a professor of bioengineering, genetics and medicine at Stanford University School of Medicine. This "may be one of the first widely used examples of pharmacogenetics -- the use of genetic information to make better prescribing decisions," he said.

Because an effective dose of warfarin can vary as much as 10-fold from one person to the next, doctors start most people on a low dose and increase it until blood tests indicate the dose is correct. That process can take months.

For the study, which is published in the Feb. 19 issue of the New England Journal of Medicine, researchers collected demographic and genetic data on people at risk for stroke, heart disease and other problems related to blood clotting. The ideal doses of warfarin for these individuals had already been established by trial and error.

In addition, they looked at variants of two genes: CYP2C9, which affects how the liver activates and excretes warfarin, and VKORC1, which activates vitamin K, essential for blood clotting.

They used the data to create an algorithm that would predict the ideal dose of warfarin in a study of more than 4,000 people.

The researchers found that the algorithm predicted the ideal dose of warfarin better than other approaches.