New Gene Research May Improve Use of Anti-Coagulant Drug

ST. LOUIS -- Each year, doctors start about 2 million Americans on the anti-coagulant drug warfarin (Coumadin), making it one of the most commonly prescribed medications.

It's also one of the hardest to administer. Countless patients can tell you war stories of running back and forth to doctors for three weeks or more until they finally get the dosage right.

New research -- done partly at Washington University here -- may change that. By looking at just two of a patient's genes, doctors more quickly and accurately may be able to estimate the right dose.

It's yet another example of using a person's unique genetic information to provide more precise individualized care. The study from the International Warfarin Pharmacogenetics Consortium is published in today's New England Journal of Medicine.

Doctors prescribe warfarin to prevent blood clots or reduce the risk of stroke in patients with atrial fibrillation or artificial heart valves and those with a history of blood clots in the legs and lungs. It also may be prescribed after joint replacement surgery.

"Unfortunately, getting the warfarin dose right is like walking a tightrope -- it's very easy to give too little or too much," said Dr. Brian F. Gage, who directs the outpatient Anticoagulation Service at Barnes-Jewish Hospital.

"If the warfarin dose is too high, patients are at risk of hemorrhage. If it's too low, they risk blood clots that can lead to stroke, heart attack or even death."

Recently Gage and several colleagues developed what they say is an improved dosing formula by analyzing a patient's genetic makeup. They look specifically at two genes involved in the body's sensitivity to and processing of warfarin. Dosing is then based on which of three variations of the genes a patient has.

The doctors say their work was borne out in an international study involving more than 5,000 patients who had been prescribed warfarin in the past and had achieved a stable dose.

They found that in 60 percent of the patients, the gene-based formula came closer to the final effective dose than the current method, which is based solely on such characteristics as age, race, body size and other medications being taken. It also proved better at identifying patients who required particularly low or high doses of the drug.

The test, which can be performed routinely at most large hospitals, currently can cost up to $400, although doctors hope the price will fall if it becomes more routine. The cost of the test also has to be weighed against a potential drop in doctor's visits required -- and the health dangers of inaccurate dosing.

Washington University now will take part in a new nationwide trial comparing the two methods. It will start late next month and involve 1,200 patients; to enroll a patient starting warfarin, doctors can call (314) 454-8638.