Anti-Cholesterol Drug Cuts Heart Attacks, Study Shows : Health: Pravastatin reduced risks for healthy men, research finds. Experts predict new era in prevention.
Men who have never had heart disease can sharply reduce their incidence of heart attacks and death by taking drugs that lower cholesterol, according to a new finding in Scotland that promises to end controversy about the approach.
Dr. James Shepherd of the University of Glasgow and Royal Infirmary reported Wednesday at the American Heart Assn. meeting in Anaheim that the drug pravastatin reduced heart attacks 31%, deaths from coronary artery disease 28% and deaths from all causes 22% over the five-year course of the so-called West of Scotland Study.
Previous studies of similar cholesterol-lowering drugs have shown that they reduce heart attacks and deaths by as much as two-thirds among men who already had heart disease.
But smaller studies among healthy men had been inconclusive about the benefits of the drugs and had suggested that they might increase death rates from cancer, violence and suicide.
The current study showed “no difference” in the rate of side effects among the 3,302 men who received pravastatin and the 3,293 who received a placebo, Shepherd said, and no increase in deaths attributable to the drug. The study looked only at men, who die of heart disease at a much higher rate than women, but the findings are expected to apply to women as well.
The only significant adverse effect might be on the pocketbooks of users because the drug costs about $45 a month in the dosages used in the study.
The results, which also appear in today’s New England Journal of Medicine, “are important because they show the treatment to be safe in a population at relatively low risk of coronary heart disease,” said Dr. Terje R. Pedersen of Aker Hospital in Oslo. He headed the pioneering, so-called “4S Study” of heart attack victims that also showed a significant improvement in survival produced by a similar drug.
“The benefits of reducing cholesterol are now established beyond reasonable doubt,” Pedersen said Wednesday.
“This is really a breakthrough for us,” said Dr. Suzanne Oparil, past president of the American Heart Assn. “It shows for the first time that cholesterol-lowering in people without heart disease will prevent heart attacks and save lives.”
The new study is particularly important, said Dr. Stuart M. Cobbe of the University of Glasgow, “because in 25% to 30% of individuals, the first clinical sign of heart disease is fatal”--typically a killer heart attack. “That’s why we want to prevent heart disease rather than treat it once it has shown itself.”
Heart disease is the leading cause of death in the United States, killing more than 923,000 people each year. High cholesterol is a major risk factor for the disease: As many as 85% of people who have a heart attack have high cholesterol levels, according to the National Institutes of Health. Other risk factors include smoking, high blood pressure, increasing age and being male.
Most physicians recommend changes in lifestyle to treat such patients, and Shepherd agrees. “Diet is always the first choice” for treatment, he said.
But too often, patients who lower cholesterol by diet backslide. Others are never able to display the will to change their lifestyle and diet. “The West of Scotland Study says that if you have to go to drugs, they will provide benefits,” Shepherd said.
“This is the beginning of a new era in which we will treat blood cholesterol levels as aggressively as we now treat hypertension,” Pedersen said.
Perhaps even more so, Shepherd said. “If I had to choose between treating my own moderate hypertension and my moderately elevated cholesterol, I would choose the cholesterol-lowering drug,” he said. “The risk reduction is actually greater.”
Pravastatin is one of a family of new cholesterol-lowering drugs that also includes lovastatin, simvastatin and fluvastatin. Lovastatin, the first of them, was isolated from a fungus and blocks the action of an enzyme that is crucial to the synthesis of cholesterol in the body. The others are chemically modified versions that bind to the enzyme more tightly, thereby blocking its function more effectively.
The research was conducted in Scotland, in part, because the incidence of high cholesterol there is very similar to that in the United States. Shepherd and his colleagues initially interviewed more than 80,000 men, asking all to go on a cholesterol-lowering diet.
Eventually, they selected a total of 6,595 men between the ages of 45 and 65 who had cholesterol levels between 250 and 300 milligrams per deciliter of blood and who could not control it by diet. Half the men received pravastatin (sold by Bristol-Myers Squibb as Pravachol) and half received a placebo.
On average, pravastatin reduced blood cholesterol levels 28%. There were 73 deaths from all cardiovascular causes in the control group, compared to 50 in the group that received pravastatin. In comparison, there were 62 deaths from all other causes in the placebo group and 56 in the pravastatin group.
“For every 1,000 men treated, we avoided 20 heart attacks, seven deaths from heart disease, two deaths from other causes and 22 major surgeries,” such as angioplasty and bypass, Shepherd said. “In the United States, that would have a major impact on costs” of heart disease.
One criticism of the study is that it did not include women. Shepherd said that is because women have only about one-quarter the risk of heart disease as men of comparable age, and because the researchers wanted to maximize the number of potential heart events to help demonstrate whether the drug was effective.
But Pedersen noted that about 20% of the subjects in last year’s 4S Study were women and that the drug was just as effective for them as for men. “There is no reason to believe that the situation will be any different in this case,” he said.
