Scandinavian researchers have produced the first long-term evidence that lowering cholesterol levels with drugs can substantially increase survival in patients who have already had a heart attack or who have heart disease.
The five-year study of nearly 4,500 patients between the ages of 35 and 70 showed that those who took the drug simvastatin were 43% less likely to die of heart disease, 34% less likely to suffer a nonfatal heart attack or other "coronary event" and 37% less likely to require a coronary artery bypass or other invasive procedures, the researchers will report today at a meeting of the American Heart Assn. in Dallas.
Equally important, those who successfully lowered their cholesterol were no more likely to die of other causes, including cancer, suicide and violence, as had been suggested by some earlier studies.
The results were so dramatic that the study was ended prematurely and the drug offered to all those receiving a placebo.
The findings appear to confirm the role of cholesterol as a major risk factor in heart disease. More than 85% of the 12 million Americans with heart disease have high cholesterol levels, according to the National Institutes of Health, and as many as 6 million could potentially benefit from use of the drug. Heart disease is the leading cause of death in the United States, killing more than 923,000 people each year.
"This study is unique because it is the first to conclusively demonstrate improved survival--people living longer," said Dr. Terje R. Pedersen of Aker University Hospital in Oslo, a co-leader of the study.
"Over the next five years," said his colleague, Dr. John Kjekahus of the University of Oslo, "we expect these findings to have a tremendous impact on standard treatment for heart attack and angina patients." In terms of reducing risk, he said, "Taking simvastatin is just as important as quitting smoking."
"This is a landmark study," said Dr. Roger Illingworth of the Oregon Health Sciences University, one of the few outside researchers familiar with the results. "If you take a population with heart disease and moderate elevations of cholesterol and give them this drug, the patients live longer and you don't increase the risk of other side effects. That is a very important finding. . . . And the longer you give the drug, the greater the benefit."
The study provides a strong message for the public and physicians, said Dr. James Cleeman, coordinator of the National Cholesterol Education Project at the National Heart, Lung and Blood Institute. High cholesterol levels in heart disease patients, he said, should be treated aggressively with diet therapy and, if that fails, with drugs.
Whether with diet or drugs, he added, lowering cholesterol can save lives. "The payoff seems quite clear."
Simvastatin, manufactured by Merck & Co., is one of a family of chemically similar cholesterol-lowering drugs that also includes lovastatin and pravastatin. Lovastatin, the best known, is isolated from a fungus and blocks the action of an enzyme that is crucial to the synthesis of cholesterol in the body. Simvastatin is a chemically modified variant of lovastatin that binds to the enzyme more tightly, thereby blocking its function more effectively. Simvastatin has been available in Europe since 1988 and in the United States since 1991.
Most previous studies have been performed with lovastatin, which lowers cholesterol levels by about 10%, according to the National Institutes of Health. "We've had small studies before that have shown that lowering cholesterol produces significant benefits . . . but the data wasn't conclusive and it didn't show a significant trend toward reduced mortality," Cleeman said.
The new, larger study found that simvastatin reduced cholesterol 25% and lowered low-density lipoprotein (LDL), the so-called bad cholesterol, by 35%. "This is the most effective cholesterol-lowering agent we know of," Pedersen said.
The researchers recruited 7,027 patients who had had a heart attack or unstable angina and who had cholesterol levels in the range 212 to 309 milligrams per deciliter of blood. All patients were given dietary advice and sent home for two months to see if they could reduce those levels. Those who could not and were medically approved were enrolled in the study.
Half the 4,444 participants received dietary intervention and simvastatin. The other half received dietary intervention and a placebo. The participants were monitored for an average of 5.4 years, and the researchers will continue to monitor them in the future.
In the study, 256 patients in the placebo group died, compared to 182 in the drug group, a 29% reduction. In the placebo group, 189 died of coronary causes, compared to 111 in the drug group. Also in the placebo category, 622 suffered either fatal or major, nonfatal heart attacks, compared to 431 in the simvastatin group.