Lower Dose of Anti-Clotting Drug Saves Lives

Reduces recurrence of deep vein thrombosis

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HealthDay Reporter

MONDAY, Feb. 24, 2003 (HealthDayNews) -- The dosage of an anti-clotting drug given to people with deep vein thrombosis can be lowered substantially without reducing its effectiveness.

That is the finding of a trial study on warfarin (also known as Coumadin) that was cut short because of its impressive results.

The trial results will be published April 10 in The New England Journal of Medicine. However, the journal says the results are being made available to doctors now "because of the study's therapeutic implications."

This "is going to save a number of lives," says study leader Dr. Yves Rosenberg, a project officer at the National Heart, Lung, and Blood Institute, which funded the research.

That's because it moves the pivot of the delicate balancing act that doctors do when they treat the disorder, Rosenberg says.

Too little warfarin, a blood thinner, can lead to recurrent blood clots that at the least cause severe discomfort and at the worst kill the patient by going to the lungs and blocking the pulmonary artery. On the other hand, too much of the drug can cause bleeding that, in the worst case, occurs in the brain and can be fatal. As many as 60,000 Americans are killed each year by these pulmonary embolisms, Rosenberg says.

"This is a huge problem, because about 2 million people in the United States suffer from this condition," says Dr. Andrew Shafer, chairman of the department of medicine at the University of Pennsylvania, who wrote an editorial that will accompany the printed report. It tends to occur in younger people, he says. Its cause is unknown, but "a majority, may even all, seem to have an inherited tendency," Shafer says.

The study enrolled 508 patients in the United States, Canada and Switzerland who were at high risk because they had an episode of deep vein thrombosis or pulmonary embolism in the previous two years. (It was supposed to include 750 patients, but was ended when analysis showed impressive results.)

The standard treatment for patients suffering from an episode of deep vein thrombosis or pulmonary embolism is five to 10 days of heparin, a clot preventer given by injection, followed by three to six months of a relatively high dose of warfarin designed to produce a blood-clotting level of 2.0 to 3.0 in what is called the international normalized ratio (INR). In the study, some patients were given low doses of warfarin, just enough to achieve an INR of 1.5 to 2.0 -- an apparently small difference, but very important clinically. Others were given a placebo.

In an average follow-up of more than four years, only 14 of the 255 patients getting low-dose warfarin had another episode, compared to 37 of the 253 placebo patients -- a reduction of 64 percent. There were four deaths in the low-dose warfarin group and eight in the placebo group, a reduction of nearly half.

Just as important, the incidence of bleeding complications in both groups was similar, the researchers report. This means patients can be kept on low-dose warfarin for much longer than is now done, which gives them longer-term protection. "Long-term, low-intensity warfarin therapy can be readily implemented in clinical practice," the report says.

Other studies will be done to see whether the warfarin dose can be reduced even further, Shafer says. However, what is really needed, he says, is a new kind of anti-clotting drug that can distinguish between harmful clots and the kind the body produces normally in response to injury. Until that comes along, he says, "we will continue to walk the tightrope of anticoagulant dosing."

More information

You can get a primer on thromboembolism from the American Heart Association or the University of Michigan.

SOURCES: Yves Rosenberg, M.D., project officer, National Heart, Lung, and Blood Institute, Bethesda, Md.; Andrew Schafer, M.D., chairman, department of medicine, University of Pennsylvania School of Medicine, Philadelphia; April 10, 2003, The New England Journal of Medicine

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