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  Vol. 291 No. 9, March 3, 2004 TABLE OF CONTENTS
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Effect of Intensive Compared With Moderate Lipid-Lowering Therapy on Progression of Coronary Atherosclerosis

A Randomized Controlled Trial

Steven E. Nissen, MD; E. Murat Tuzcu, MD; Paul Schoenhagen, MD; B. Greg Brown, MD; Peter Ganz, MD; Robert A. Vogel, MD; Tim Crowe, BS; Gail Howard, MS; Christopher J. Cooper, MD; Bruce Brodie, MD; Cindy L. Grines, MD; Anthony N. DeMaria, MD; for the REVERSAL Investigators

JAMA. 2004;291:1071-1080.

Context  Statin drugs reduce both atherogenic lipoproteins and cardiovascular morbidity and mortality. However, the optimal strategy and target level for lipid reduction remain uncertain.

Objective  To compare the effect of regimens designed to produce intensive lipid lowering or moderate lipid lowering on coronary artery atheroma burden and progression.

Design, Setting, and Patients  Double-blind, randomized active control multicenter trial (Reversal of Atherosclerosis with Aggressive Lipid Lowering [REVERSAL]) performed at 34 community and tertiary care centers in the United States comparing the effects of 2 different statins administered for 18 months. Intravascular ultrasound was used to measure progression of atherosclerosis. Between June 1999 and September 2001, 654 patients were randomized and received study drug; 502 had evaluable intravascular ultrasound examinations at baseline and after 18 months of treatment.

Interventions  Patients were randomly assigned to receive a moderate lipid-lowering regimen consisting of 40 mg of pravastatin or an intensive lipid-lowering regimen consisting of 80 mg of atorvastatin.

Main Outcome Measures  The primary efficacy parameter was the percentage change in atheroma volume (follow-up minus baseline).

Results  Baseline low-density lipoprotein cholesterol level (mean, 150.2 mg/dL [3.89 mmol/L] in both treatment groups) was reduced to 110 mg/dL (2.85 mmol/L) in the pravastatin group and to 79 mg/dL (2.05 mmol/L) in the atorvastatin group (P<.001). C-reactive protein decreased 5.2% with pravastatin and 36.4% with atorvastatin (P<.001). The primary end point (percentage change in atheroma volume) showed a significantly lower progression rate in the atorvastatin (intensive) group (P = .02). Similar differences between groups were observed for secondary efficacy parameters, including change in total atheroma volume (P = .02), change in percentage atheroma volume (P<.001), and change in atheroma volume in the most severely diseased 10-mm vessel subsegment (P<.01). For the primary end point, progression of coronary atherosclerosis occurred in the pravastatin group (2.7%; 95% confidence interval [CI], 0.2% to 4.7%; P = .001) compared with baseline. Progression did not occur in the atorvastatin group (–0.4%; CI –2.4% to 1.5%; P = .98) compared with baseline.

Conclusions  For patients with coronary heart disease, intensive lipid-lowering treatment with atorvastatin reduced progression of coronary atherosclerosis compared with pravastatin. Compared with baseline values, patients treated with atorvastatin had no change in atheroma burden, whereas patients treated with pravastatin showed progression of coronary atherosclerosis. These differences may be related to the greater reduction in atherogenic lipoproteins and C- reactive protein in patients treated with atorvastatin.


Author Affiliations: Departments of Cardiovascular Medicine (Drs Nissen, Tuzcu, Schoenhagen, and Mr Crowe) and Diagnostic Radiology (Dr Schoenhagen), Cleveland Clinic Lerner School of Medicine, Cleveland, Ohio; Department of Medicine, University of Washington, Seattle (Dr Brown); Department of Medicine, Brigham and Women's Hospital, Boston, Mass (Dr Ganz); Department of Medicine, University of Maryland, Baltimore (Dr Vogel); Pfizer Inc, New York, NY (Ms Howard); Department of Medicine, Medical College of Ohio, Toledo (Dr Cooper); LeBauer Cardiovascular Research Foundation, Greensboro, NC (Dr Brodie); Cardiac Catheterization Laboratory, Division of Cardiac Diseases, William Beaumont Hospital, Royal Oak, Mich (Dr Grines); and Department of Medicine, University of California, San Diego (Dr DeMaria).


RELATED LETTERS

Aggressive Lipid-Lowering Therapy and Regression of Coronary Atheroma
Uffe Ravnskov and Morley C. Sutter
JAMA. 2004;292(1):38.
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Aggressive Lipid-Lowering Therapy and Regression of Coronary Atheroma
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Aggressive Lipid-Lowering Therapy and Regression of Coronary Atheroma
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Aggressive Lipid-Lowering Therapy and Regression of Coronary Atheroma
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Aggressive Lipid-Lowering Therapy and Regression of Coronary Atheroma—Reply
Steven Nissen and For the REVERSAL Investigators
JAMA. 2004;292(1):39-40.
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High-Intensity Statin Treatment for Coronary Heart Disease
Frank M. Sacks
JAMA. 2004;291(9):1132-1134.
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