THE EFFECT OF SIMVASTATIN ON PROGRESSION OF CORONARY-ARTERY DISEASE -THE MULTICENTER CORONARY INTERVENTION STUDY (CIS)

Background In several angiographic trials, HMG-CoA reductase inhibitor s 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 art ery disease progression. The question remains however, whether higher dosages of simvastatin would be more advantageous in respect to the ma gnitude of the effect and the required time interval to demonstrate tr eatment efficacy. Methods and results In the Coronary Intervention Stu dy (CIS), a multicentre randomized double-blind placebo-controlled stu dy, the effects of lipid-lowering therapy with simvastatin on progress ion of coronary artery disease in 254 men with documented coronary art ery disease and hypercholesterolaemia were investigated. Following a p eriod of lipid-lowering diet, treatment with 40 mg simvastatin or plac ebo was maintained for an average of 2.3 years. Two primary angiograph ic endpoints were chosen: the global change score (visual evaluation a ccording 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 simv astatin group showed a 35% LDL-cholesterol decrease. Coronary angiogra phy was repeated in 205 patients (81%) and 203 film pairs (80%) were e valuable by quantitative coronary angiography. In the simvastatin and placebo groups, the mean global change scores were +0.20 and +0.58 res pectively, demonstrating a significantly slower progression of coronar y artery disease in the treatment group (P=0.02). The change in minimu m lumen diameter assessed by computer-assisted quantitative evaluation with the CAAS I system was -0.02 mm in the simvastatin group and -0.1 0 mm in the placebo group (P=0.002). In the simvastatin group, there w as a significant correlation between the LDL cholesterol levels achiev ed therapeutically and the per patient mean loss of minimum lumen diam eter (r=0.29; P=0.003). During the study period, there was no signific ant difference in the incidence of serious cardiac events (15 of 129 p atients in the simvastatin group and 19 of 125 patients in the placebo group, ns). Conclusion Treatment with 40 mg simvastatin.day(-1) reduc es serum cholesterol and slows the progression of coronary artery dise ase significantly within a short period of treatment time. In the trea tment group, retardation of progression is inversely correlated to the LDL-cholesterol levels achieved.