CLINICAL RESEARCH: CLINICAL INSIGHTS FROM CARDIAC IMAGING
Effects of Aggressive Versus Conventional Lipid-Lowering Therapy by Simvastatin on Human Atherosclerotic Lesions
A Prospective, Randomized, Double-Blind Trial With High-Resolution Magnetic Resonance Imaging
Roberto Corti, MD*, ,1,
Valentin Fuster, MD, PhD, FACC,
Zahi A. Fayad, PhD,
Stephen G. Worthley, MD*,,
Gerard Helft, MD, PhD*,,
William F. Chaplin, PhD,
Jörg Muntwyler, MD1,
Juan F. Viles-Gonzalez, MD*,,
Jesse Weinberger, MD ,
Donald A. Smith, MD,
Gabor Mizsei, MSEE and
Juan J. Badimon, PhD, FACC*,,*
* Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New York, New York
Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York
Department of Neurology, Mount Sinai School of Medicine, New York, New York
Manuscript received November 1, 2004;
revised manuscript received March 18, 2005,
accepted March 22, 2005.
* Reprint requests and correspondence: Dr. Juan J. Badimon, Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, One Gustave Levy Place, P.O. Box 1030, New York, New York 10029 (Email: juan.badimon{at}mssm.edu).
OBJECTIVES: This study sought to compare the effects of aggressive and conventional lipid lowering by two different dosages of the same statin on early human atherosclerotic lesions using serial noninvasive magnetic resonance imaging (MRI).
BACKGROUND: Regression of atherosclerotic lesions by lipid-lowering therapy has been reported.
METHODS: Using a double-blind design, newly diagnosed hypercholesterolemic patients (n = 51) with asymptomatic aortic and/or carotid atherosclerotic plaques were randomized to 20 mg/day (n = 29) or 80 mg/day (n = 22) simvastatin. Mean follow-up was 18.1 months. A total of 93 aortic and 57 carotid plaques were detected and sequentially followed up by MRI every six months after lipid-lowering initiation. The primary MRI end point was change in vessel wall area (VWA) as a surrogate for atherosclerotic burden.
RESULTS: Both statin doses reduced significantly total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) versus baseline (p < 0.001). Total cholesterol decreased by 26% versus 33% and LDL-C by 36% versus 46% in the conventional (20 mg) versus aggressive (80 mg) simvastatin groups, respectively. Although the simvastatin 80-mg group had significantly higher baseline TC and LDL-C levels, both groups reached similar absolute values after treatment. A significant reduction in VWA was already observed by 12 months. No difference on vascular effects was detected between the randomized doses. Post-hoc analysis showed that patients reaching mean on-treatment LDL-C  100 mg/dl had larger decreases in plaque size.
CONCLUSIONS: Effective and protracted lipid-lowering therapy with simvastatin is associated with a significant regression of atherosclerotic lesions. No difference in vessel wall changes was seen between high and conventional doses of simvastatin. Changes in vessel wall parameters are more related to LDL-C reduction rather than to the dose of statin.
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Abbreviations and Acronyms
| | CHD = coronary heart disease | | HDL = high-density lipoprotein | | IVUS = intravascular ultrasound | | LA = lumen area | | LDL-C = low-density lipoprotein cholesterol | | MRI = magnetic resonance imaging | | TC = total cholesterol | | TE = echo time | | TR = repetition time | | TVA = total vessel area | | VWA = vessel wall area | | VWT = vessel wall thickness |
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