EFFICACY AND SAFETY OF SIMVASTATIN IN PRIMARY HYPERCHOLESTEROLEMIA

An open multicenter study was conducted in 1090 patients with primary hypercholesterolemia (plasma total cholesterol greater-than-or-equal-to 2.5 g/l) to evaluate the efficacy and safety of simvastatin in hypercholesterolemia with an inadequate response to a low-fat diet. A low-fat diet was initiated or continued in every case. Lipid-lowering drugs were discontinued six weeks before inclusion into the treatment period. Simvastatin was given once daily, in the evening, for 12 weeks. The starting dosage of 10 mg/day was doubled after the fourth week in patients who still had a total cholesterol level greater-than-or-equal-to 2.5 g/l or a low density lipoprotein (LDL) cholesterol level greater-than-or-equal-to 1.6 g/l. The diet was continued throughout the study. At the end of the 12-week treatment period, there were significant reductions (P < 0.001) in the levels of total cholesterol (- 23.6%), LDL cholesterol (- 32.8 %), and triglycerides (- 17.2 %), as well as a significant (P < 0.001) 10.1% increase in the level of high-density lipoprotein (HDL) cholesterol. After 4 weeks, the simvastatin dosage was increased to 20 mg/day in 47.9% of patients. At the end of the study, 82% of patients had a total cholesterol level under 2.5 g/l and 75% an LDL cholesterol level under 1.60 g/l. Simvastatin was well tolerated. Clinical treatment-related adverse events were reported in 6.8% of patients and consisted mainly of gastrointestinal complaints (3.7%) and muscular symptoms (1.5%). Treatment-related laboratory test abnormalities were found in 1.3% of patients and consisted of elevations in transaminase levels (0.5%) or gamma-GT levels (0.1%) and elevations in creatine phosphokinase levels without concomitant muscular symptoms (0.7%). Only 1.6% of patients were withdrawn from the drug. These data confirm the efficacy and favorable clinical and laboratory test safety profile of simvastatin in clinical practice.