A randomized, open-label, comparative study of simvastatin plus diet versus diet alone on angiographic retardation of coronary atherosclerosis in adult Japanese patients: Japanese utilization of simvastatin therapy (JUST) study

Abstract

Background: Cholesterol-lowering therapy reduces the risk of cardiovascular events by slowing the progression or enhancing the regression of coronary atherosclerosis. Objective: This study assessed the effects of simvastatin 10 mg/d on progressive coronary atherosclerosis in Japanese patients with coronary artery disease and mild to moderate hypercholesterolemia. Methods: In a 2-year, open-label comparative study, patients with coronary atherosclerotic lesions (⩾50% diameter stenosis) and serum total cholesterol levels ⩾200 and ⩽280 mg/dL were randomly assigned to 2 groups: 1 group received simvastatin 10 mg/d taken orally with diet (S-D) and the other group was assigned to diet alone (D). Atherosclerotic progression in coronary segments was compared in the 2 groups using quantitative coronary angiography (QCA). QCA measurements were done under blinded conditions. The study's primary end point was the comparison of mean changes in each segment's minimum obstruction diameter (MOD) or mean segment diameter (MSD) between the S-D group and the D group. Results: A total of 299 patients were randomized, 146 to the S-D group and 153 to the D group. Mean (SD) age was 58.7 (8.0) years and mean (SD) total cholesterol level was 232.6 (21.6) mg/dL at baseline. After 2 years, serum low-density lipoprotein cholesterol levels decreased by 31.9% in the S-D group and by 2.0% in the D group. QCA showed significant stenotic progression in the D group, with reductions in MOD and MSD both by per-segment-based ( P < 0.001 and P = 0.004, respectively) and per-patient-based (both P = 0.004) analyses. Although simvastatin treatment suppressed atherosclerotic progression in both per-segment- and per-patient-based analyses, significant reductions were found only in MOD values with per-segment-based analyses ( P = 0.034). In a categorical approach, progression was found in significantly fewer segments in the S-D group compared with the D group (MOD, P = 0.014; MSD, P = 0.003), with odds ratios (S-D) group/D group) of 0.571 for MOD and 0.390 for MSD. Significantly fewer patients with angiographic progression were observed in the S-D group (23.3%) compared with the D group (39.4%) with respect to MSD ( P = 0.02). Conclusion: Two years of treatment with simvastatin 10 mg/d improved patients' lipid profile and retarded coronary atherosclerotic progression in Japanese patients with coronary artery disease and mild to moderate hypercholesterolemia.