Study Challenges Cholesterol Recommendations

Finds intensive statin therapy saves heart patients

MONDAY, March 8, 2004 (HealthDayNews) -- The "miracle" cholesterol-lowering drugs called statins have just become more miraculous.

New research shows high levels of the drugs given to people who have just been hospitalized with heart attacks or high-risk unstable angina not only prevented future "events" but also saved lives.

These findings call into question current guidelines on how low low-density lipoprotein (LDL, or the "bad" cholesterol) levels should be.

"This will have a major impact in the real world," says Dr. Eric Topol, chairman of the department of cardiovascular medicine at the Cleveland Clinic Foundation. "It was striking how fast it was. It was a whopping benefit and unexpected. This changes everything."

Topol wrote an editorial that accompanies the study in the April 8 issue of the New England Journal of Medicine. The journal released the study early to coincide with a presentation March 8 at a meeting of the American College of Cardiology in New Orleans.

In his editorial, Topol writes that "in the management of atherosclerotic vascular disease, statin drugs have already surpassed all other classes of medicine in reducing the incidence of the major adverse outcomes of death, heart attack and stroke."

In earlier trials, statins were able to reduce LDL cholesterol levels by 25 percent to 35 percent.

"The basis of our study was that statins were tested and were very, very effective," says Dr. Christopher P. Cannon, corresponding author of the study and a cardiologist at Brigham and Women's Hospital in Boston. But the drugs had not yet been tested in a hospital setting in people who were seriously ill.

The current paper set out to answer two questions, Cannon says. The first was whether statins would be effective in heart attack patients in a hospital setting. The second and bigger question was whether it would be worth it to lower cholesterol levels by 50 percent, instead of the 25 percent already demonstrated.

Current guidelines from the National Cholesterol Education Program recommend that LDL cholesterol levels be less than 100 milligrams per deciliter of blood for patients with established coronary artery disease or diabetes. These researchers wanted to know if even lower was even better.

The answer to both questions, it turned out, was yes.

The trial involved 4,162 patients at 349 sites in eight countries. All of the participants had been hospitalized within the past 10 days with either a heart attack or high-risk, unstable angina. One group was given 40 milligrams of pravastatin each day (the standard therapy), while the other was given 80 milligrams of atorvastatin each day (intensive therapy).

In the standard therapy group, the mean LDL cholesterol level attained was 95 mg per deciliter. In the intensive group, it went down to 62 mg per deciliter. These differing levels corresponded to different outcomes. Over a period of about 24 months, the intensive therapy group (atorvastatin) showed a 16 percent lower risk of overall major cardiovascular events and a 28 percent reduction in death. Every outcome measured was better in the intensive group, except for stroke, which was about the same in both groups. Even though the groups were followed for about two years, the benefit was seen extremely quickly, in less than 30 days.

The surprising results suggest that ideal LDL cholesterol level should be quite a bit lower than currently recommended.

"The control group was getting gold-standard excellent care but this still added benefit," Cannon says. "One surprising thing was how quickly it happened."

The downside of this more intensive treatment is minimal, Cannon adds. "We have to be a little cautious on the liver," he says. About 1 percent of the control group and 3 percent of the intensive therapy group experienced liver problems. In the real world, it will probably be higher.

Which brings doctors to the next question: How easily and quickly will these results be translated into the real world?

"Hopefully the very clear results will mean that people going home from the hospital will get this treatment," Cannon says.

But even today, as the editorial points out, only about 11 million people are getting statins when an estimated 36 million should be on them. Worldwide, more than 200 million people meet the criteria for treatment with statins while only 25 million are actually taking the drugs.

This is largely a cost issue, Topol states. His editorial points out that in Cleveland, the cost of 10 mg of atorvastatin per day (the recommended starting dose) is $900 per year, while the 80-mg dose costs $1,400 per year. At a collective $12.5 billion, statins are the largest prescription drug expenditure in the United States, he writes.

"It's going to take a while to assimilate," Topol says. "There's a cost issue. That is why people don't take statins today."

More information

For more on cholesterol, visit the American Heart Association or the National Cholesterol Education Program.

SOURCES: Christopher P. Cannon, M.D., cardiologist, Brigham and Women's Hospital, Boston; Eric Topol, M.D., chairman, department of cardiovascular medicine, Cleveland Clinic Foundation, Cleveland; April 8, 2004, New England Journal of Medicine
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