• Roberto Corti, Valentin Fuster, Zahi A Fayad, Stephen G Worthley, Gerard Helft, William F Chaplin, Jörg Muntwyler, Juan F Viles-Gonzalez, Jesse Weinberger, Donald A Smith, Gabor Mizsei, and Juan J Badimon.
• Cardiovascular Biology Research Laboratory, Mount Sinai School of Medicine, New York, New York 10029, USA.
• J. Am. Coll. Cardiol. 2005 Jul 5; 46 (1): 106-12.

ObjectivesThis 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).BackgroundRegression of atherosclerotic lesions by lipid-lowering therapy has been reported.MethodsUsing 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.ResultsBoth 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 < or = 100 mg/dl had larger decreases in plaque size.ConclusionsEffective 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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