By Rob Stein
Washington Post Staff Writer
Tuesday, March 14, 2006
A cholesterol-lowering drug has for the first time been shown to shrink the kinds of blockages that cause most heart attacks, indicating that such pills may offer the first non-surgical way to start to clear clogged arteries.
A study of more than 500 patients found that high doses of a "statin" drug began to reverse the buildup, causing plaques lining the artery walls to recede. Statins are already widely used to prevent or slow heart disease.
"This may be the beginning of a real revolution in the treatment of heart disease," said Steven E. Nissen of the Cleveland Clinic, who led the study released yesterday. "We're not merely slowing down the inexorable progression but truly reversing the disease. It's very exciting."
Some experts criticized the study, saying the researchers failed to compare patients who received the intensive treatment with those who did not. Consumer advocates and other researchers have also raised safety concerns about the statin used in the study, Crestor.
While Nissen and other experts agreed that more research is needed to confirm the findings, determine whether the shrinkage will translate into fewer heart attacks and strokes, and make sure high doses of the potent drugs can be administered safely, they said the findings could mark an important step forward. The findings are likely to accelerate the trend of doctors using cholesterol drugs much more aggressively, they said.
"This is very exciting for those of us who take care of patients," said Roger S. Blumenthal of the Johns Hopkins University School of Medicine. "This is the first study showing you can take a pill for two years and get some actual reversal of disease. It really supports aggressive treatment."
Heart disease, the nation's leading killer, occurs when plaques build up inside artery walls. The accumulations can burst, forming clots that block blood flow to the heart and brain, causing heart attacks and strokes. Patients take statins to slow or even stop the narrowing of arteries and can undergo surgical procedures to bypass or reopen clogged arteries. But there has been no way to reverse the disease.
"That's always been just a dream -- actually making the disease go away," Nissen said.
In their study, Nissen and his colleagues gave 507 patients with mild to moderate heart disease the maximum dose of Crestor -- 40 milligrams. The drug caused low-density lipoprotein (LDL) cholesterol levels to drop from about an average of 130.4 to 60.8, a 53 percent reduction and the biggest drop ever shown in a study. LDL is the "bad" cholesterol that accumulates inside artery walls. At the same time, the patients' high-density lipoprotein (HDL) levels rose from an average of 43.1 to 49, a jump of nearly 14.7 percent. HDL is called the "good" cholesterol because it helps remove LDL from the blood.
When researchers compared ultrasound tests of the arteries of 349 patients before and after two years of treatment, they found the volume of plaque inside their arteries had diminished by between 6.9 and 9.1 percent, the researchers reported at a meeting of the American College of Cardiology in Atlanta.
"Many people thought, and I was among them, that we really weren't going to be able to reverse the disease with statin drugs. The thinking was if you got the bad cholesterol low enough you wouldn't form new plaque, but you couldn't get rid of the plaque that was already there," Nissen said. "But we showed you could. I was very surprised."
The only other study to reduce plaque used a substance that boosted HDL levels. But the effect was much smaller and the drug was much more difficult to administer.
The new study, which will appear in the April 5 issue of the Journal of the American Medical Association, was funded by the drug's maker, AstraZeneca, but was conducted independently, Nissen said.
Consumer advocates and other researchers have raised concerns about whether Crestor causes serious kidney and muscle problems. In this study, the drug appeared as safe as other drugs in this class, which are generally considered to be well tolerated, Nissen said. But he acknowledged more research is needed to make sure it or other statins at high doses could be used safely to drive cholesterol to very low levels.
Several studies are testing whether intensive therapy with other possibly safer statins would have the same effects, either used alone, in combination with other cholesterol drugs or with drugs that boost HDL levels.
Other researchers said the findings add to the growing body of evidence that it is beneficial to drive cholesterol levels as low as is safely possible.
"This is a proof-of-principle study," said Elizabeth G. Nabel, director of the National Heart, Lung and Blood Institute. "It adds the next chapter in the story of lowering cholesterol."
Nabel and others cautioned, however, that it remains to be seen whether shrinking plaque will actually reduce the number of heart attacks and strokes. It may be the stability of the plaque, not its size, that is important, some experts said.
"The prevailing theory is that what happens is statins make unstable plaque . . . less likely to rupture, and that is the way the benefit is derived," said James I. Cleeman of the National Cholesterol Education Program.
In addition, some researchers criticized the study for failing to compare patients to others taking a placebo or less intensive statins.
"That kind of analysis, where you don't have any kind of control group, is full of potential problems," said Frank Sacks of the Harvard School of Public Health. "There is no way to know really what is going on."
Nissen agreed that more research is needed to establish that shrinking plaque translates into saving lives. But he argued that there is good evidence to suspect it would, and he defended the decision to compare the patients in the study to themselves, saying it was sufficient to demonstrate an effect.