CHOLESTEROL DRUG CUTS HEART-ATTACK RISK, STUDY SHOWS.

Byline: Gina Kolata The New York Times

A new study provides the first evidence that people with average cholesterol levels can substantially reduce their risk of heart attack by taking a drug that drives their cholesterol levels even lower.

The study, financed by Merck & Co., involved 6,605 middle-age men and women, half of whom took Merck's powerful and expensive cholesterol-lowering drug, lovastatin; the rest took a dummy pill. After five years, those who had taken lovastatin had 37 percent fewer heart attacks and other serious signs of heart disease than those who had taken the placebo.

Medical experts said the study was well-conducted and that its results are solid. Dr. Claude Lenfant, director of the National Heart, Lung and Blood Institute, described it as ``a great study.''

But already the results are opening a debate among medical experts: How hard should people try to reduce their cholesterol levels below what is now considered acceptable? And how much should the nation pay to save a few more people from heart disease?

In their paper, being published today in The Journal of the American Medical Association, the authors said that if the study's findings were put into practice, the eligible population for cholesterol-lowering drugs would triple, going from the 2 million who qualify for drug treatment today to 6 million adult Americans. An editorial accompanying the paper said the annual cost of the drug for just 1,000 patients over a five-year period would be $1.42 million, not including the costs of doctor visits and laboratory tests.

Many doctors themselves, who heard the study results when they were reported at a meeting of the American Heart Association in November, already have begun taking the drugs, called statins. One who is not taking the drug said he used to ask his doctor friends if they were taking a statin. Now, he said, the more appropriate question is, ``Which statin are you taking?''

Medical experts said doctors' prescribing patterns are hard to know, but that at least some appear to be prescribing statins for people with average cholesterol levels. Dr. Jeffrey Isner, chief of vascular medicine and cardiovascular research at St. Elizabeth's Hospital in Boston and a referral specialist who speaks to cardiologists daily, said some doctors are being very aggressive about prescribing the drugs and have told him so.

Dr. Antonio M. Gotto Jr., dean of the Weill Medical College of Cornell University and a lead author of the paper, said he hopes the study will ``redefine what we consider normal.'' He said that until now no one was giving statins to people like those in the study because medical experts thought it probably wouldn't do any good.

The study, Gotto said, shows that perception is not correct. He added that lovastatin is due to go off patent in 2001, which should lower its cost.

But some, like Dr. Alan Garber, director of the Center for Primary Care and Outcomes Research at Stanford University, are uneasy with prescribing statins for so many people at relatively low risk of heart disease. Yes, he said, the drugs seem safe in short-term studies. And yes, some studies with very high-risk groups have found that statins can prevent deaths.

But, he said, there is no information on whether there are long-term side effects of taking statins. For people with high cholesterol levels, the benefits of the drugs outweigh the uncertainty about medical complications that could occur many years later, Garber said. But that might not be true for people with average cholesterol levels, he said.

Current guidelines for cholesterol lowering, determined by the National Heart, Lung and Blood Institute, use cholesterol levels, age, sex and the presence or absence of other factors like high blood pressure and cigarette smoking to determine who should take a cholesterol-lowering drug. Although most of the study participants had one or more risk factors for heart disease other than cholesterol levels, most did not have levels high enough to warrant medical treatment under those guidelines.

The study involved 5,608 men ages 45 to 73 and 997 women ages 55 to 78 who had no signs or history of heart disease. Their average cholesterol level was 221 milligrams per deciliter of blood, which put them smack in the middle of the American cholesterol range, in the 51st percentile, the researchers reported. But their levels of high-density lipoproteins, or HDL, the cholesterol carriers that protect against heart disease, were low.

After five years, 183 people taking the dummy pill had had a heart attack or other serious symptom of heart disease. But just 116 of those taking lovastatin, or 37 percent fewer, had had such a heart disease symptom.

The lovastatin effect began appearing in the first year of the study, Gotto said, and held up. ``We were very pleasantly surprised, as you can imagine,'' he said. Also, ``we did not find any safety concerns.''

Gotto added that the drug was so effective that it essentially wiped out the adverse effect of having another risk factor for heart disease. For example, if a person in the study smoked cigarettes and took lovastatin, his or her risk became that of someone with the same cholesterol level who did not take the drug and did not smoke.

The study was not designed to look for differences in mortality rates, and so it remains possible that even if the drugs reduce the number of heart attacks in people with average cholesterol levels, they might not save lives.

Leading heart disease experts commended the findings. Heart disease remains the leading cause of death in this country, killing 500,000 a year. And 1.5 million Americans have heart attacks each year.

Heart institute director Lenfant praised the research and said that if he had cholesterol levels in the range of those of the people in the study and had even one other condition - like cigarette smoking, high blood pressure, a family history of heart disease or diabetes - that increased his chances of developing heart disease, he would take a statin himself.

But Dr. Thomas A. Pearson, chairman of the department of community medicine at the University of Rochester School of Medicine, wrote an editorial asking the thorny question of how much this benefit is worth. Pearson said in an interview that since there seem to be so many who could benefit from statins, ``some of my more exuberant colleagues are talking of putting this in the water supply.''

Facetiousness aside, he added, the drugs cost a great deal - $900 to $1,800 a year, depending on the dose - and many must take them in order for a few to benefit.

Pearson noted that if 1,000 people like those in the study took lovastatin for five years, 12 heart attacks would be prevented, as would seven cases of unstable angina, which is a type of chest pain that indicates severe heart disease. In addition, 17 operations to open blocked blood vessels would be avoided.