Research Shows Statin Reverses Heart Disease

CHICAGO _ High doses of a statin drug that dramatically lowers the harmful type of cholesterol while significantly increasing the helpful type has for the first time reversed heart disease by a small but significant degree, a Cleveland Clinic researcher reported Monday.

A two-year study of 349 patients found the statin, Crestor, reduced low-density lipoprotein, the so-called bad cholesterol, by 53.2 percent and increased high-density lipoprotein by 14.7 percent, according to a report released online by the Journal of the American Medical Association and presented at the American College of Cardiology conference.

Crestor caused cholesterol-filled fatty deposits in coronary arteries to shrink by 7 to 9 percent, said the study’s lead author, Dr. Steven E. Nissen, interim chairman of cardiovascular medicine at the Cleveland Clinic and incoming president of the college of cardiology.

“It’s always been the hope that if we gave powerful enough cholesterol lowering drugs, that we could at least partially reverse the plaque buildup in the coronary arteries,” he said in a telephone interview. “Until now we really haven’t been able to achieve that goal.”

Dr. Roger S. Blumenthal, director of the Johns Hopkins Preventive Cardiology Center, said, “This is the first study that shows with a single agent that we actually have the potential to modestly reduce atherosclerosis.”

Writing in an accompanying editorial, Blumenthal said there are a number of ongoing studies with new drugs that can raise HDL even higher. “This (the Nissen study) gives us some hope that maybe we really will be able to see more significant reversal of atherosclerosis.

“The results of several ongoing trials will help determine what agent or combination of pharmacologic agents is most efficacious in the long-term management of at-risk patients,” he said. Heart attacks are the No. 1 cause of death in the United States.

Doctors in 1987 first started prescribing cholesterol-lowering statin drugs, which have since become the most widely prescribed class of drugs in the country. Studies show statins reduce the risk of heart attack and stroke by 25 percent to 35 percent. Earlier studies showed the drugs could slow and even halt the progression of plaque buildup in coronary arteries. A study by Nissen and his colleagues showed another statin, Lipitor, reversed hardening of the arteries in a few patients, but the finding was inconclusive.

“This study confirms prior work that really aggressive lipid lowering with statin drugs does lead to slowing of atherosclerosis,” said Dr. Robert Bonow, chief of cardiology at Northwestern Memorial Hospital and co-director of its Bluhm Cardiovascular Institute. “The important thing here is that it’s actually showing for the first time regression of atherosclerosis.”

Dr. Angelo Scanu, director of the University of Chicago’s lipid clinic, said that while the results appear promising, further testing is necessary to document the reversal benefits of Crestor. Patients should not rush to their doctors seeking changes in their statin medications, he said.

“Using a single dose of a powerful statin in a given group of people would appear to be beneficial,” he said. “However, other statins may be able to do the same, maybe with a lesser dose.”

Exactly how statins reduce the risk of heart disease is not known, but the drugs perform a number of complex operations. Lowering LDL means there is less circulating in the blood to become impacted in arterial linings. One role of HDL is to extract cholesterol out of plaques, a job that may become more efficient with higher HDL levels. Statins also reduce vascular inflammation, which has been linked to heart disease.

AstraZeneca, the maker of Crestor, paid for the study, but the trial was carried out independently with Cleveland Clinic having full control over the findings, Nissen said. Nissen said any consulting fees he receives from drug companies are automatically given to charity.

Pfizer, the maker of another statin, Lipitor, and Merck, maker of Zocor, are funding studies of their compounds combined with newer agents designed to boost levels of HDL. Lipitor, the most widely prescribed drug in the country, has annual sales of about $13 billion compared with about $4 billion annual sales for Crestor.

The Cleveland Clinic study showed that Crestor lowered average levels of LDL from 130.4 milligrams per deciliter to 60.8 while elevating average HDL levels from 43.1 mg/dl to 49.0. Regression of atherosclerosis occurred in 63.6 percent of the patients. Patients in the study took 40 milligrams of Crestor, which is the highest dose doctors prescribe. Typically physicians prescribe 5, 10 or 20 milligrams.

Side effects were minimal, Nissen said, about the same as with other statin drugs. Approximately 1 percent of patients on statins experience muscle pain or abnormal liver enzymes. Both conditions are reversible when the drug is stopped.

Longtime Crestor critic Dr. Sidney M. Wolfe, director of Public Citizen’s Health Research Group, issued a statement reiterating the group’s claim that Crestor has unique risks without unique benefits and that the drug should not be prescribed. The same regression of atherosclerosis can most likely be achieved with other statins with a better safety record, Wolfe said.

The level of LDL considered safe has been steadily falling. The National Cholesterol Education Program Adult Treatment Panel in 2004 recommended patients with high heart disease risk should lower their LDL below 100 milligrams per deciliter and consideration should be given to lowering it to about 70.

Nissen measured plague shrinkage with a technique called intravenous ultrasound, or IVUS. A tiny ultrasound emitter is inserted into coronary arteries to provide images of the interior lining of the vessels, where cholesterol plaques build up.

“These patients had a lot of reduction in plaque volume,” Nissen said. “The ability to turn back the clock on this disease is a pretty important concept.”

University of Chicago cardiologist Dr. Matthew Sorrentino said further studies would be needed to determine if reducing plaque size would prevent more heart attacks and strokes.

“We’ve been looking for the type of therapy that will actually regress the disease, make the disease go away,” Sorrentino said. “This doesn’t make the disease go away, but it’s a step in reducing the disease burden and that might be very important.”

The American Heart Association estimates that 71 million Americans have heart disease, which is responsible for 1.2 million heart attacks each year and 480,000 deaths.

___

(c) 2006, Chicago Tribune.

Visit the Chicago Tribune on the Internet at http://www.chicagotribune.com/

Distributed by Knight Ridder/Tribune Information Services.

For information on republishing this content, contact us at (800) 661-2511 (U.S.), (213) 237-4914 (worldwide), fax (213) 237-6515, or e-mail reprints@krtinfo.com.