Simvastatin in the treatment of patients with hypercholesterolemia and associated coronary heart disease risk factors: An Italian multicenter study

Abstract Hyperlipidemia has a pivotal role in the development of atherosclerosis and its complications, especially when additional coronary heart disease (CHD) risk factors are present. The development of drugs that inhibit cholesterol synthesis may help in the treatment of high-risk patients. The aim of the present study was to evaluate the efficacy, tolerability, and safety of simvastatin in patients with mild-to-moderate hypercholesterolemia and associated CHD risk factors. Of the 307 patients who were enrolled in this study on the basis of a 6-week preliminary screening phase, 296 completed a 48-week active treatment period. Simvastatin was started at 10 mg/d. Thereafter, the dose was adjusted every 4 weeks to reach the goal of a total plasma cholesterol concentration ⩽200 mg/dL. At the end of the study, 47.2% of the patients were being treated with simvastatin 10 mg/d, 44% with 20 mg/d, and 8.8% with 40 mg/d. During the active treatment period, total plasma cholesterol concentration was reduced by 30.9% and low-density lipoprotein cholesterol by 41.8%. Plasma triglycerides also decreased during the study (11.1%), whereas high-density lipoprotein cholesterol increased (13.0%). Elevations in plasma transaminase concentrations not greater than three times the upper limit of normal were observed in only three patients and spontaneously regressed without discontinuing simvastatin therapy. These increases were not associated with jaundice or other clinical signs or symptoms. Three patients had serum creatine phosphokinase concentrations slightly higher than the upper limit of normal but experienced no associated symptoms. Clinical adverse experiences were limited both in frequency and severity. Only 3 patients discontinued treatment because of adverse experiences. These findings suggest that simvastatin is an effective and generally well-tolerated cholesterol-lowering agent in the treatment of hypercholesterolemic patients with associated CHD risk factors.