Copyright © 1997 by the European Society of Cardiology.
© 1997 The European Society of Cardiology
The effect of simvastatin on progression of coronary artery disease
The Multicenter Coronary Intervention Study (CIS)
*Herz-Zentrum Bad Krozingen Leichlingen, Germany
Fachklinik Rhein-Ruhr, Essen-Kettwig Leichlingen, Germany
Klinik Roderbirken, Klinik für Herz- und Kreislauferkrankungen der LVA Rheinprovinz Leichlingen, Germany
Klinik Höhenried für Herz- und Kreislaufkrankheiten der LVA obb. Bernried, Germany
||Centre Hospitalier Universitaire Vaudois (CHUV) Lausanne Germany
¶Universität Freiburg Germany
**Technische Universität München Germany
revised 26 January 1996; accepted 29 March 1996.
Correspondence: H.-P. Bestehorn, Herz-Zentrum Bad Krozingen, Südring 15, 79189 Bad Krozingen, Germany
Abstract
BACKGROUND: In several angiographic trials, HMG-CoA reductase inhibitors have shown a beneficial effect on the progression of coronary artery disease. Using 20 mg simvastatin day–1, a treatment period of up to 4 years was necessary to show a significant reduction in coronary artery disease progression. The question remains however, whether higher dosages of simvastatin would be more advantageous in respect to the magnitude of the effect and the required time interval to demonstrate treatment efficacy.
METHODS AND RESULTS: In the Coronary Intervention Study (CIS), a multicentre randomized double-blind placebo-controlled study, the effects of lipid-lowering therapy with simvastatin on progression of coronary artery disease in 254 men with documented coronary artery disease and hypercholesterolaemia were investigated. Following a period of lipid-lowering diet, treatment with 40 mg simvastatin or placebo was maintained for an average of 2·3 years. Two primary angiographic endpoints were chosen: the global change score (visual evaluation according to the method of Blankenhorn) and the per patient mean change of minimum lumen diameter (evaluated by the CAAS I system).
The mean simvastatin dose was 34·5 mg day–1. In the placebo group, the serum lipids remained unchanged; in comparison to the placebo group the simvastatin group showed a 35% LDL-cholesterol decrease. Coronary angiography was repeated in 205 patients (81%) and 203 film pairs (80%) were evaluable by quantitative coronary angiography. In the simvastatin and placebo groups, the mean global change scores were +0·20 and +0·58 respectively, demonstrating a significantly slower progression of coronary artery disease in the treatment group (P=0·02). The change in minimum lumen diameter assessed by computer-assisted quantitative evaluation with the CAAS I system was –0·02 mm in the simvastatin group and –0·10 mm in the placebo group (P=0·002). In the simvastatin group, there was a significant correlation between the LDL cholesterol levels achieved therapeutically and the per patient mean loss of minimum lumen diameter (r=0·29; P=0·003). During the study period, there was no significant difference in the incidence of serious cardiac events (15 of 129 patients in the simvastatin group and 19 of 125 patients in the placebo group, ns).
CONCLUSION: Treatment with 40 mg simvastatin day–1 reduces serum cholesterol and slows the progression of coronary artery disease significantly within a short period of treatment time. In the treatment group, retardation of progression is inversely correlated to the LDL-cholesterol levels achieved.
Key Words: Atherosclerosis • simvastatin • hydroxymethyl-glutaryl-CoA reductase inhibitors • progression • coronary artery disease • quantitative angiography
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