2002-12-17 11:01:00
By Merritt McKinney

NEW YORK (Reuters Health) - Study after study has shown that cholesterol-lowering drugs called statins can prevent heart attacks, but in a new trial the statin pravastatin (Pravachol) did not reduce the risk of death and heart disease in people with moderately high cholesterol and high blood pressure.

But the results of the study do not mean that pravastatin or other statins cannot prevent heart disease, the study's lead author told Reuters Health.

In an interview, Dr. Barry R. Davis explained that pravastatin was effective at lowering cholesterol in a wide range of people in the study. But participants who did not take the statin but who instead received "usual care"--which could also include cholesterol-lowering medication--also experienced a drop in cholesterol, said Davis, who is at the University of Texas-Houston Health Science Center. The differences in how much cholesterol dropped in each group "were not big enough" to show an effect on heart disease and other clinical outcomes, Davis said.

Statins' record in clinical trials is impressive, but many groups of people, including women, older people, racial and ethnic minorities and people with diabetes, were not adequately represented in earlier studies. The new study, which drew participants from a larger study of treatments for high blood pressure, was designed to see how well a statin could prevent deaths in a wide variety of people.

The study included more than 10,000 people who were at least 55 years old and who had moderately high cholesterol and high blood pressure. Participants were randomly assigned to take pravastatin or to receive the "usual care" recommended by their physician. This care could include cholesterol-lowering drugs, but this was discouraged unless a person's health took a turn for the worse.

For lowering cholesterol, pravastatin was a success, according to a report in the December 18th issue of the Journal of the American Medical Association (news - web sites). Four years after the study began, total cholesterol had dropped 17% in people taking the statin and about 8% in the usual care group. And at the same time, testing of a random sample of participants showed that levels of LDL, the "bad" type of cholesterol, had dropped nearly 28% in the pravastatin group and 11% in the usual care group.

In a bit of encouraging news, Davis said, pravastatin lowered cholesterol in a wide range of people, regardless of age, sex, race or history of diabetes.

It is well known that lowering LDL cholesterol can reduce the risk of heart attack and stroke, but the study showed that people taking pravastatin were no less likely to die or develop heart disease than people receiving usual care.

These results do not mean that pravastatin does not provide clinical benefits, though, Davis said. He explained that during the course of the study, several other research teams reported studies demonstrating the powerful cholesterol-lowering effects of statins. Because of the increased awareness of statins, people in the usual care group were prescribed the cholesterol-lowering drugs "much more than we anticipated," Davis said.

The Houston researcher pointed out that cholesterol levels also dropped in the usual care group, although not as much as in people specifically assigned to take statins. Unlike in other statin trials, many of which compared the drugs to an inactive placebo, the difference may not have been big enough to detect any clinical benefits, Davis said.

The study was sponsored by the National Heart, Lung, and Blood Institute, but it also received funding from Pfizer. AstraZeneca, Pfizer and Bristol-Myers Squibb, which makes pravastatin, donated medications used in the study.

"Physicians might be tempted to conclude that this large study demonstrates that statins do not work," according to Dr. Richard C. Pasternak, of Harvard Medical School (news - web sites) in Boston, Massachusetts. "However, it is well known that they do," he concludes in an editorial that accompanies the study.

What may have happened, according to Pasternak, is that the drugs may not be as effective in ordinary settings as they are in clinical trials where participants are carefully selected and followed closely.

Pasternak has served as a consultant to or on the advisory boards of several pharmaceutical companies, including Bristol-Myers Squibb. In addition, he has received funding from Merck-Medco and has served on the speakers bureau for several drug makers.

Bristol-Myers Squibb was not available for comment at press time.

SOURCE: Journal of the American Medical Association 2002;288:1998-3007,3042-3044.