Benefits seen in larger reductions of cholesterol

Decrease reduces risk of heart attack, death, drug study suggests

March 09, 2004|By NEW YORK TIMES NEWS SERVICE

Lowering cholesterol far below the level that most doctors now consider adequate can substantially reduce patients' risk of having or dying from a heart attack, researchers reported yesterday.

The findings, cardiologists say, will greatly change how doctors treat patients with heart disease and will provide the impetus to re-evaluate how low cholesterol levels should be.

The study compared high doses of one of the most powerful cholesterol-lowering drugs, Pfizer's Lipitor, to a less potent drug, Pravachol, made by Bristol-Myers Squibb, which sponsored the trial.

The patients taking Lipitor were significantly less likely to have heart attacks or to require bypass surgery or angioplasty, the study found. Both drugs are statins, a class of medications that block a cholesterol-synthesizing enzyme. They are often prescribed for patients with heart problems.

"This is really a big deal," Dr. David Waters, a professor of medicine at the University of California at San Francisco, said of the findings. "We have in our hands the power to reduce the risk of heart disease by a lot. It's very exciting."

Reassessing standards

National guidelines call for levels of low-density lipoprotein cholesterol, which carries cholesterol to arteries, to be below 100 milligrams per deciliter in high-risk patients. But the two-year study, involving 4,162 patients hospitalized for a sudden attack of chest pain from heart disease, asked whether reducing cholesterol levels far below 100 milligrams was beneficial.

The study will be published in the April 8 issue of the New England Journal of Medicine, but the journal lifted its embargo because the results were presented at the American College of Cardiology meetings in New Orleans.

Comparison

In the study, patients were randomly assigned to take 80 milligrams a day of Lipitor, the highest available dose, or 40 milligrams of Pravachol, the highest dose when the study began. The patients' cholesterol fell within the levels specified by the national guidelines.

But on Lipitor, the patients had a median LDL level of 62, as compared with a level of 95 for those who took Pravachol.

(Although Pravachol is now available in an 80-milligram dose, experts say doubling the dose does not make much difference because it only reduces LDL levels by an additional 6 percent.)

Within a month, the Lipitor patients started doing better than those taking Pravachol.

Dr. Eric J. Topol, a cardiologist at the Cleveland Clinic Foundation, called the findings a sea change.

"It's a big shake-up," Topol said. "It's a whole different viewpoint on what statins can do."

Even though the Pravachol patients would, until now, have been considered adequately treated, their rate of heart attacks, bypass surgery and angioplasty; symptoms such as chest pain; and events such as strokes and death was 26.3 percent, as compared with 22.4 percent with Lipitor, a difference of about 16 percent.

The death rate for Lipitor patients was 28 percent lower than for those taking Pravachol, and the death rate from cardiovascular disease was 30 percent lower among the Lipitor patients.

Unexpected findings

Researchers said they were particularly surprised because Bristol-Myers Squibb, which sponsored the study, had expected it to show that Pravachol was as effective as Lipitor. The researchers, at Harvard Medical School, specified in their contract with Bristol-Myers Squibb that they would publish the results no matter how they came out.

Heart disease experts complained that the study would not show any difference because it had only half of the number of patients that would be needed and followed them for only half the time.

"A lot of people believed that lower is better," observed Dr. Daniel Rader, director of the Preventive Cardiology and Lipid Clinic at the University of Pennsylvania. "But no one thought that this would be the study to prove it."

Dr. Steven Nissen, a cardiologist at the Cleveland Clinic, said drug companies "never ever sponsor a trial like this that they think has a chance of going the wrong way." But, he added, "this trial backfired because in fact the differences between these two drugs are very profound."

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