The drugs can cut heart and stroke risks in people with normal cholesterol levels, researchers say
By Thomas H. Maugh II 16 nov 2008--In results from an eagerly anticipated study that could dramatically change the treatment of cardiovascular disease, researchers have found that statin drugs -- now given to millions of people with high cholesterol -- can halve the risk of heart attacks and stroke in seemingly healthy patients as well.
The study of nearly 18,000 people with normal cholesterol found that the drugs, already among the most widely prescribed in the country, also lowered the risk of death from heart disease by 20%, suggesting that millions more people should be put on a daily regimen.
The effects were so beneficial that the planned four-year study was halted after less than two years, researchers said Sunday at a New Orleans meeting of the American Heart Assn.
"These are very, very dramatic findings," said Dr. Elizabeth G. Nabel, director of the National Heart, Lung and Blood Institute.
Nabel, who was not involved in the research, noted that the institute already had an expert panel revising guidelines for treatment and prevention of heart disease and that the new results were likely to be included in its recommendations.
The revision would most likely call for testing a wide range of healthy people with a simple blood test for above-normal levels of a compound called C-reactive protein, which indicates increased arterial inflammation that can be treated with statins.
The new study focused on a specific drug -- rosuvastatin, sold as Crestor by drug maker AstraZeneca, which funded the research.
But Dr. Tim Gardner of the Christiana Care Health System in Wilmington, Del., and president of the American Heart Assn., said, "This is likely to be a class effect, not a specific drug effect. This is a win for all statins, I would say."
The new treatment could prevent 50,000 heart attacks, strokes and deaths each year if it were widely adopted, experts said.
The findings "really change what we are going to do in the future," said Dr. W. Douglas Weaver of Henry Ford Hospital in Detroit and president of the American College of Cardiology. "This targets a patient group that normally would not be screened or treated to prevent cardiovascular disease."
Critics, however, charged that such wide use would cost the U.S. healthcare system more than $9 billion a year at a time when healthcare costs are climbing dramatically and could expose large numbers of people to potential side effects.
Crestor is one of the most expensive statins, costing about $3.45 a day, but generic statins typically sell for less than $1.
About 120 people would have to take the drugs for two years to prevent one heart attack, stroke or death, Dr. Mark Hlatky of Stanford University wrote in an editorial accompanying the report, which was published online Sunday by the New England Journal of Medicine.
Nonetheless, the findings will most likely be widely adopted soon, Gardner said.
"It will be incorporated into practice guidelines after all the nuances are sorted out," he said.
Statins, first introduced in 1987, block the production of cholesterol in the liver. High cholesterol is a major risk factor for heart attacks and stroke because it contributes to the buildup of plaque that blocks arteries, preventing oxygenated blood from reaching the heart and brain.
An estimated 450,000 Americans die of heart disease each year and an additional 150,000 from strokes.
More than 13 million Americans take statins regularly, and worldwide sales total more than $22 billion a year, the bulk of that in the United States.
But doctors have long been mystified by the fact that about half of heart attacks occur in patients with normal cholesterol levels, and researchers have been looking for other important risk factors.
Three years ago, Dr. Paul Ridker of Brigham and Women's Hospital in Boston and his colleagues studied results from clinical trials in which statins had been used to treat high cholesterol levels and concluded that, in addition to their cholesterol-lowering ability, the drugs also reduced arterial inflammation, which can lead to the buildup of plaque.
The finding was part of a series of studies that showed statins have a number of beneficial effects beyond their ability to reduce cholesterol. Several reports have shown that they also help prevent glaucoma and cataracts and inhibit dementia.
Others suggest that they also moderate the symptoms of multiple sclerosis and increase bone density. These benefits may be related to their ability to reduce inflammation.
C-reactive protein, or CRP, has long been associated with inflammation. Very high levels of CRP are associated with arthritis and other autoimmune diseases. But slightly elevated levels -- about a hundredth of the levels seen in arthritis -- have been linked to inflammation in the arteries that causes cardiovascular diseases.
In the new trial, called Jupiter, Ridker and his colleagues studied 17,802 patients with normal cholesterol levels and elevated CRP, as measured by a test called high-sensitivity CRP, on which Ridker and his hospital hold the patent.
Men in the study were over 50; women were over 60. About 7,000 of the patients were women and 5,000 were minorities -- both groups that have not received much attention in previous statin trials.
Half of the patients received 20 milligrams of rosuvastatin and half a placebo.
"We specifically chose rosuvastatin because it is the most potent of the statins," said Ridker, who has worked as a consultant to AstraZeneca and other pharmaceutical companies. "We got very large effects on both [cholesterol] and CRP."
Low-density lipoproteins, the so-called bad cholesterol, were reduced by 50%, and CRP was reduced by 37%.
Patients receiving rosuvastatin had a 54% lower risk of heart attacks, a 48% lower risk of stroke and a 46% lower risk of requiring either angioplasty or bypass surgery, Ridker said.
There were 136 heart-related problems a year for every 10,000 people taking the placebo, compared with 77 for those taking rosuvastatin.
"This is very good news for these populations," Ridker said.
The primary side effect was a slight increase in newly diagnosed diabetes among those taking the drug, an increase that has also been noted in previous trials of statins.
Experts believe that the benefits of a regimen of statins for the targeted patient group outweigh any increase in side effects.
"This will become an important part of the armamentarium of the primary care doctor," Weaver said. "I see this as being part of that panel of preventions that they will be applying in men over 50 and women over 60."
The CRP test costs about $80.
Dr. James Stein and Dr. Jon Keevil of the University of Wisconsin, Madison, estimate that about 4% of the adult U.S. population, about 7.4 million people, fit the criteria to receive the test.