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Combining Drugs Doesn't Improve Arterial Disease Outcome

WEDNESDAY, July 18 -- Adding a blood thinner to standard clot-preventing medications did not ease the devastating toll of peripheral arterial disease (PAD), the blockage of a blood vessel in an arm or leg that often is the prelude to a heart attack or stroke, an international study has found.

It was a disappointment, because earlier studies found the combination of the clot-preventing drug, either aspirin or Plavix, with the blood thinner Coumadin, brought benefits to people who suffered heart attacks, said study author Dr. Sonia S. Anand, an associate professor of medicine at McMaster University in Hamilton, Ontario. The report is published in the July 19 issue of the New England Journal of Medicine.

"The primary measures of outcome in the study were heart attack, stroke or death," Anand said. "We did not observe a difference in the rates of outcome. What we found was an increase in bleeding complications in the patients who got the combination."

The trial followed 2,161 people with PAD in Canada and Europe for an average of 35 months. The incidence of heart attack, stroke or cardiovascular deaths was 15.9 percent among those getting aspirin plus Coumadin and 17.4 percent among those getting only aspirin. The difference was too small to reach statistical significance and was offset by the 4 percent incidence of life-threatening bleeding in those getting combination therapy, compared to 1.2 percent among those getting only aspirin.

The hope was that the combination of drugs that act in different ways to prevent formation of clots that can block arteries would reduce the risk for people with PAD, said Dr. Emile R. Mohler III, an associate professor of medicine at the University of Pennsylvania, who wrote an accompanying editorial.

Aspirin and other drugs such as Plavix prevent the activation of platelets, blood cells that join to form clots. Coumadin prevents formation in the liver of the molecular factors that accelerate clot formation.

"Unfortunately for PAD patients, this study shows that Coumadin is not a drug that will help them in the long run," Mohler said.

For the time being, single-drug treatment with a medication that acts against platelets will continue to be the mainstay of PAD therapy, both Anand and Mohler said.

Anand said she would use aspirin first, in part because it is much less expensive than Plavix. One trial has shown that Plavix "is just mildly more effective," she said, adding she might switch to that drug depending on the results of aspirin therapy in individual patients.

The field of clot-preventing medication is an active area of pharmaceutical research, Mohler said.

"Doctors are desperate for a drug to replace Coumadin," he said. "It is a lifesaving drug, but it is extremely annoying to use because of all the precautions that must be taken, including watching your diet."

People who take Coumadin are cautioned about their intake of green leafy vegetables. They are rich in vitamin K, which affects formation of blood-clotting factors in the liver.

Researchers also are trying to develop new antiplatelet agents that could replace aspirin or Plavix, Mohler said.

When and if such drugs come along, the results of the study indicate that caution is advisable, Anand said. "All these trendy new blood thinners," she said. "Before anyone thinks they can be used with patients with PAD, they would have to do the appropriate controlled trial."

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Posted: July 2007