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

https://doi.org/10.1016/j.jacc.2005.03.054Get rights and content
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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.

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

Cited by (0)

This study was supported by grants from the National Institutes of Health (HL54469, Drs. Fuster and Badimon); the National Heart, Lung, and Blood Institute (HL61801, Dr. Fuster); The Swiss National Research Foundation (Dr. Corti); The National Heart Foundation of Australia (Dr. Worthley); The French Federation of Cardiology (Dr. Helft); and Merck and Co, Inc. Merck and Co. was partially responsible for the funding of the project. Mount Sinai authors are fully responsible for data acquisition, evaluation, and writing the manuscript without any interference from the funding sources.

1

Drs. Corti and Muntwyler are currently working in the Department of Cardiology, University Hospital Zurich, Switzerland.