News Release

Intensive statin therapy reduces amount of plaque buildup in arteries compared to moderate treatment

Peer-Reviewed Publication

JAMA Network

Patients with coronary heart disease who received intensive lipid-lowering treatment had less progression of coronary atherosclerosis (plaque buildup in the arteries) than patients treated with a moderate lipid-lowering regimen, according to a study in the March 3 issue of The Journal of the American Medical Association (JAMA).

According to background information in the article, statin drugs (lipid-lowering medications) have been shown to reduce both atherogenic (development of plaque in arterial walls) lipoproteins and cardiovascular illness and death. However, the optimal approach and target level for lipid reduction with statins in patients with established coronary artery disease (CAD) remains uncertain.

Steven E. Nissen, M.D., of the Cleveland Clinic Lerner School of Medicine, Cleveland, and colleagues compared the effects of two statin regimens. The Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study was a double-blind, randomized trial at 34 centers in the United States. Intravascular ultrasound, which provides detailed images within a blood vessel, was used to measure plaque buildup in the wall of the coronary arteries.

Between June 1999 and September 2001, 654 patients were randomized and received a study drug; 502 had intravascular ultrasound examinations at baseline and after 18 months of treatment. Patients were randomly assigned to receive a regimen designed to moderately reduce low-density lipoprotein cholesterol (LDL-C) using 40 mg of pravastatin, or an intensive LDL-C lowering regimen, using 80 mg of atorvastatin.

The researchers found that patients with moderate cholesterol levels who received 18 months of intensive lipid-lowering therapy had greater reductions in LDL-cholesterol than patients who received the moderate lipid lowering regimen, and also had greater reductions in C-reactive protein (a measure of inflammation). Patients in the intensive therapy group also showed significantly less progression of coronary atherosclerosis in comparison with patients who received a more moderate regimen. The change in volume of plaque buildup was positive in the pravastatin group (2.7 percent), indicating net progression compared with the baseline measurement, whereas in the atorvastatin group, the change was negative (-0.4 percent), showing no disease progression since baseline.

"These findings have potential implications for treatment guidelines for patients with dyslipidemia and established CAD," the authors write. "A more intensive lipid-lowering therapy is required than is currently recommended by national and international guidelines to obtain maximal reduction in the progression of coronary atherosclerosis," the researchers conclude.
(JAMA. 2004;291:1071-1080. Available post-embargo at JAMA.com.)

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Editor's Note: The study was funded by Pfizer. For the financial disclosures of the authors, please see the JAMA article.

EDITORIAL: HIGH-INTENSITY STATIN TREATMENT FOR CORONARY HEART DISEASE

In an accompanying editorial, Frank M. Sacks, M.D., of the Harvard School of Public Health, Brigham and Women's Hospital, and Harvard Medical School, Boston, writes that a policy to use the highest statin doses as standard therapy has implications for cost and potential adverse effects.

"The vast majority of clinical and research experience is with conventional statin doses, which have provided a deservedly positive view of statin therapy. To put maximal statin therapy, such as with 80 mg of atorvastatin or 40 mg of rosuvastatin, on the same footing of clinical confidence requires results from large long-term clinical trials. Fortunately, several large trials comparing intensive with conventional statin therapy are near completion and results are expected soon," he writes.

"Until the results of these studies are available, it is prudent to treat any high-risk patient, as defined by national guidelines, with a statin at an intensity appropriate to achieve the recommended goals for LDL-C. In addition, with this focus on LDL-C reduction, clinicians must not lose sight of the need to manage other established cardiovascular disease risk factors including hypertension and atherogenic dyslipidemia, manifested by low levels of high-density lipoprotein cholesterol and high levels of triglycerides. At least as important, this concentration on drug treatment should not deflect attention from diet and lifestyle interventions that have the potential even with moderate improvements to reduce cardiovascular disease incidence by between 75 percent and 80 percent," he concludes.
(JAMA. 2004;291:1132-1134. Available post-embargo at JAMA.com)

Editor's note: Dr. Sacks is a consultant for the following companies: Abbott, AstraZeneca, Bristol-Myers Squibb, Fournier, Kos, Kowa, Lilly, Pfizer, Reliant and Sankyo.


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