February 19, 2009

Genetic Makeup May Dictate Patients’ Warfarin Dose

A new formula that involves gene testing could equip doctors with a better means of gauging the dosage of the common blood-thinning drug warfarin, according to a new large-scale study.

Warfarin is one of the most widely prescribed drugs in the world "“ an estimated 2 million Americans with heart conditions or other risk factors begin taking the drug each year "“ but doctors currently use a method of trial and error to determine how much a patient should be taking.

This method can be dangerous - if the patient receives a dose that is too high, they could bleed profusely. On the other hand, if it's too low, they could develop deadly clots.

Researchers have pinpointed two genes - CYP2C9 and VKORC1 "“ which can indicate how an individual will react to warfarin. Researchers from more than 20 teams in nine countries formed the International Warfarin Pharmacogenetics Consortium (IWPC) to investigate whether or not a person's genetic makeup could be used to indicate their level of warfarin dosage.

Researchers collected data and had access to anonymized information from about 5,700 people from countries including Taiwan, Japan, Korea, Singapore, Sweden, Israel, Brazil, Britain and the United States on stable dosages of warfarin.

Data for each patient included demographic information like age, gender and race; CYP2C9 and VKORC1 variants; and initial, as well as optimized, warfarin dosages, researchers said.

Patients who begin taking warfarin typically start with 5 milligrams a day. But the proper amount for one patient may be 10 times as much as what's best for another, researchers told the AP.

"You need to be just right," Donna Arnett, a researcher of genetic testing and cardiovascular health at the University of Alabama at Birmingham, who wasn't involved in the study, told the AP.

Researchers found that the genetic testing method was accurate in setting the right warfarin dose amount in about 1 in 3 patients.

Researchers did not take into account the side effects or consider how tobacco and alcohol use might figure into blood thinner dosing.

"By sharing information and expertise, the consortium researchers developed a way to dose warfarin that is based on data from patients around the world," said Dr Jeremy M. Berg, director of the National Institute of General Medical Sciences (NIGMS), which supported the study.

"This is a highly commendable example of international cooperation and data sharing and should increase the potential utility of the results."

"People will go to their doctors and ask" about genetic tests, Berg said.

However, he told the AP that until the larger study is completed, "it's unlikely that very many places will offer this."

In August 2007, the FDA approved updated labeling for warfarin, also known as Coumadin, "to explain that people's genetic makeup may influence how they respond to the drug," based on studies that found people reacted differently to the drug based on certain gene variations.

"Today's approved labeling change is one step in our commitment to personalized medicine. By using modern science to get the right drug in the right dose for the right patient, FDA will further enhance the safety and effectiveness of the medicines Americans depend on," Dr Andrew C. von Eschenbach, Commissioner of Food and Drugs, said in an August 2007 statement.

"With growing evidence on how certain genes affect the way individual patients respond to warfarin, we are now ready to move forward with a major clinical trial to test these strategies in patients who are starting warfarin therapy," said Dr Elizabeth G. Nabel, director of The National Heart, Lung and Blood Institute (NHLBI).

Dr. Frank M. Torti, acting commissioner of Food and Drugs, said: "The NIH research is precisely what is needed to advance the promise of personalized medicine, ensuring that patients receive the safest and most effective drug dose."


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