The drug combination not only didn't help most people in a newly released study, but it unexpectedly almost doubled the risk of death, heart attack or stroke for those with no clogged arteries but with worrisome conditions like high blood pressure and high cholesterol.

"They actually were harmed," said Dr. Eric Topol. "This was a trial to determine the boundaries of benefit, and it did. You don't use this drug for patients without coronary artery disease."

Expression of Concern

Nothing in the study changes recommendations that people who recently have had heart attacks or a procedure to unclog an artery take those medicines. This study dealt with expanding use of the drug to other people.

Topol and Dr. Deepak Bhatt of the Cleveland Clinic led the study, which involved 15,603 people in 32 countries. Topol has since left the clinic and is at Case Western Reserve University in Cleveland.

Results were reported Sunday at an American College of Cardiology conference whose organizers issued an "expression of concern" saying the drug's maker, Sanofi-Aventis SA, told some stock analysts the results of the study in advance, in violation of the conference's embargo policies.

However, Sanofi spokesman Michel Joly denied the claim Sunday, saying the company provided no results in advance.

Aspirin's ability to prevent heart attacks in men is legendary but it does little for their risk of stroke. In women, aspirin wards off strokes but only reduces heart attack risk in those 65 or older. Adding Plavix to aspirin for people being treated for a heart attack cuts their risk of a second one or death.

For these reasons, doctors thought the drug combination might prevent "heart attacks waiting to happen" in people with very clogged arteries or lots of risk factors like heavy smoking, diabetes and high cholesterol.

They gave everyone in the study low daily doses of aspirin plus Plavix or a dummy pill and looked at how they fared more than two years later.

Plavix Should Not Be Used for Prevention

Adding Plavix made little difference for the group as a whole except for slightly reducing hospitalizations. But for the 20 percent with no signs of heart disease, the drug combination proved dangerous. Heart-related deaths almost doubled, from 2.2 percent of those taking only aspirin to 3.9 percent of those who added Plavix.

The only people even modestly helped by adding Plavix were those with established heart disease. Their risk of heart attack, stroke or death was about 7 percent versus 8 percent for those taking aspirin alone.

Specialists said this was not enough to justify recommending the drug in light of the overall findings of no benefit.

The cost and risks of Plavix don't justify expanding its use for prevention, Dr. Marc Pfeffer of Brigham and Women's Hospital in Boston and Dr. John Jarcho of the New England Journal of Medicine write in an editorial in the journal, which will be published along with the study results in the April 20 issue.

"Plavix should not be used for prevention," said Dr. Elizabeth Nabel, director of the National Heart, Lung and Blood Institute. "Aspirin alone is sufficient."

The study was paid for by Sanofi and Bristol-Myers Squibb, which sell Plavix in the United States for about $4 a pill. Outside the US the drug is sold as Iscover. Many of the researchers have ties to the companies or others that make heart drugs.

Also at the conference, the third study in roughly a year confirmed that a different strategy to prevent heart attacks -- folic acid and vitamin B supplements -- doesn't work.

These lower homocysteine, a blood substance that can make arteries stiffen and clog.

Dr. Eva Lonn of McMaster University in Hamilton, Ontario, and colleagues gave 5,522 people with clogged arteries or diabetes these vitamins or phony pills for five years. Homocysteine dropped in people given the supplements, but not the risk of heart attack or death. Vitamin takers suffered slightly fewer strokes than the others, but they also were more likely to be hospitalized for chest pains.

Results were released by the New England Journal, which will publish them in print later.