At the New England Journal of Medicine's Web site:
Certain people with normal cholesterol levels may benefit greatly from taking a statin drug, according to a new study released Sunday at the American Heart Association meeting in New Orleans.
Statin drugs are used by millions of people to reduce elevated cholesterol levels. The drugs lower the risk of heart attacks, strokes and other life-threatening events.
Now the new study shows that men and women who have normal cholesterol levels but signs of inflammation in the blood vessels can cut the risk of heart attack or stroke in half.
The data analysis, detailed in an online version of the New England Journal of Medicine, showed that 20 milligrams of Crestor, taken daily, reduced the incidence of heart attack, stroke, bypass surgery, heart pain and cardiovascular death by about half. It also reduced the number of deaths by any cause by 20 percent.
The study is already dividing the cardiology community. Some experts say the study is so convincing that cardiologists should begin testing people for signs of inflammation and, when present, begin treating them with a statin — even though the total cholesterol level is normal or even low.
But other experts are concerned that the results will be used to justify unneeded medical care.
The test for inflammation used in the study is called "hsCRP." The "hs" stands for "high-sensitivity." "CRP" is "C-reactive protein" — a protein that is found in greater quantities in the blood when there's inflammation of the vessels around the heart and other parts of the body.
A Worldwide Study
Heart researchers from 26 countries tested the drug Crestor (generic name: rosuvastatin) in 8,901 men and women with normal cholesterol levels, high hsCRP levels, and no history of heart disease. Their average age was 66.
A similar group of 8,901 people took placebos.
"When I, as a cardiologist, prescribe statins to patients with high cholesterol, I do so because I believe they'll lower the risk of a heart attack or stroke by about 20 or 25 percent," says cardiologist Paul Ridker of Brigham and Women's Hospital in Boston, who headed the study.
"What's so remarkable in these new data is that the risk reduction in these patients with high hsCRP is 45 to 50 percent — almost twice as effective," he said.
Milestone For Controversial Theory
Ridker has been working for years on the so-called "inflammation hypothesis." The idea is that high levels of CRP indicate an increased risk of heart disease, and that lowering CRP levels can decrease risk.
Ridker holds a "use patent" on CRP testing for heart disease risk. He says the patent hasn't affected his judgment and that the data speaks for itself.
The hypothesis builds on the established knowledge that a heart attack occurs when an inflamed plaque — a buildup of fat in the wall of an artery — bursts. A blood clot then forms. The clot blocks blood flow, and a heart attack or stroke ensues.
You only have to have one plaque for this to happen. That's how people with normal cholesterol levels and little buildup in their arteries can still have heart attacks.
So researchers wanted to study whether bringing down the inflammation would reduce the risk of a heart attack or stroke.
The study released Sunday was sponsored by Crestor manufacturer AstraZeneca. The results were better than Ridker expected.
"We had hoped to see perhaps a 10 or 15 percent risk reduction. That would have told us that the inflammation hypothesis did have meaning," he says. "The observation here of a 45 or 50 percent reduction is just like a gift — it's a clinical gift, it's a research gift, and we're very excited about it."
"That is a larger reduction in the things that we care the most about — morbidity and mortality — than we've ever seen in a statin trial," says Steven Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic. "And it occurred very quickly, in only 1.9 years of average duration of treatment."
The trial was stopped partway through because an independent monitoring board judged the results to be strong enough already to prove that testing and treatment work. But the early halt to the study means there are no long-term data on the safety and effectiveness of this approach.
Sidney Wolfe, with Public Citizen's Health Research Group, is concerned about studies showing an increase in the incidence of diabetes in people on statins. He's worried about the current study as well, which shows that diabetes increased from 2.4 percent in the placebo group to 3.0 percent in those taking Crestor.
In an editorial in the Journal, Mark Hlatky, a professor of medicine at Stanford University, also points out that the incidence of cardiovascular problems in people with normal cholesterol is low enough to begin with. Cutting that risk in half, he says, isn't as dramatic as it sounds.
There were 157 cardiac events among the 8,901 people in the placebo group, and 83 events in those who got Crestor, he observes.
Statins For The Healthy?
And then there's the larger question about giving drugs — for life — to otherwise healthy people.
"You're talking about 20 years of treatment," Hlatky says. "They are lowering cholesterol to levels that have not been seen in other studies, because people started low and they lowered them yet further. Is that safe for 20 years? We don't know."
It may be that people would have to take them even longer than 20 years. The study was done mainly in people who were in their 50s, 60s and 70s. But inflammation can show up decades earlier.
Other questions remain. Among them is whether Crestor is the only statin that has the effect seen in the study. It's possible that other, far cheaper statins — which have been shown to reduce CRP levels — would also work. Some are available as generics.
The National Heart, Lung and Blood Institute, part of the National Institutes of Health, has a standing committee of outside experts who establish guidelines for the treatment of heart disease. The head of NHLBI, Elizabeth Nabel, says the panel will consider the new trial when issuing its next set of guidelines on who should get tested for heart disease, and how they should be treated.