BOSTON (AP) - Steady low doses of an old-fashioned blood thinner have been shown to dramatically lower the risk of recurring, dangerous blood clots in the legs and lungs, offering the first effective treatment for an estimated 750,000 U.S. victims annually.
Until now, there has been no accepted long-term therapy to prevent these sporadic clots from coming back, as they often do. The new study, released Monday, found that a modest dose of the drug warfarin reduces this risk by two-thirds.
Warfarin, also known as Coumadin, is already the standard blood thinner for treating these clots. Typically, though, the medicine is stopped after a few months because of worry that the standard dose will trigger bleeding.
Dr. Paul Ridker of Boston's Brigham and Women's Hospital, who directed the federally sponsored study, said the treatment costs pennies a day and is easy to administer once the correct dose is determined for each patient.
"It provides an immediate new standard of care, because the current standard is no care," Ridker said. "Physicians should strongly consider switching their patients to long-term treatment to prevent these clots."
The American Heart Association estimates that each year, about 2 million people suffer a deep vein thrombosis, a clot in a vein deep in the leg. The result is painful swelling that become life-threatening if the clot floats to the lungs. This complication occurs in about 600,000 people annually, killing 60,000.
More than half of all cases result from surgery or trauma, such as broken bones, and are not likely to recur. However, Ridker estimates that 750,000 people each year have a deep vein thrombosis resulting from more obscure causes, often an inherited tendency to spontaneously form unwanted clots. Almost a third of these people get another clot within eight years.
His study compared low-dose warfarin and dummy pills in people at risk for these recurring clots. It began in 1998 and was scheduled to end in 2005. However, the early results were so dramatically positive that researchers decided it would be unethical to continue giving people placebos, so the study was stopped in December.
"This disease generally affects younger people, most of whom are otherwise healthy. The issue of how to manage it is a very, very big problem. Anything that reduces the risk is a major advance, and this is one," said Dr. Andrew Schafer, head of medicine at the University of Pennsylvania.
The results will be published in the April 10 issue of the New England Journal of Medicine. They were posted Monday on the journal's Web site.
Warfarin was introduced in 1954. (It is also a chief ingredient in rat poison.) Several new drugs are in testing that developers hope will be safer or more effective than warfarin.
The drug is initially time-consuming for doctors to prescribe, since they cannot easily figure out how much to give. Two people the same size, sex and age may require vastly different doses to achieve the same result. Doctors set the dose by testing the drug's effect on patients' blood clotting.
Ridker said that in the study, patients' doses ranged from a half milligram to 10 milligrams daily. Typically, though, patients took less than half as much as would ordinarily be given to treat deep vein thrombosis. Once the correct dose was set, doctors checked patients' clotting once every two months.
Even with the new results, some doctors questioned whether warfarin will be widely used this way.
"I think there is a lot of resistance in the medical community to using warfarin. It's not an easy drug to use. Patients have to get regular blood tests. There is a fear of bleeding," said Dr. Ira S. Nash, associate director of the cardiovascular institute at Mount Sinai Medical Center in New York City.
Ridker said a larger problem is that no pharmaceutical company will promote this new use, since the drug is generic. "If it doesn't become the standard of care, it will only be because there aren't people out their educating doctors, so to speak," he said.
The study was initially intended to enroll 750 people with an average follow-up of four years, but it was stopped after 508 patients. Repeat clots occurred in 14 people on low-dose warfarin and 37 getting dummy pills. Four people on warfarin died, as did eight in the comparison group.
The major worry was uncontrolled bleeding, especially strokes. However, the only bleeding stroke occurred in someone in the comparison group. Five people taking warfarin and two on placebos developed bleeding bad enough to require hospitalization, although all recovered.
EDITOR'S NOTE: Medical Editor Daniel Q. Haney is a special correspondent for The Associated Press.
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