EFFICACY AND SAFETY OF SIMVASTATIN IN PRI MARY HYPERCHOLESTEROLEMIA

An open multicenter study was conducted in 1090 patients with primary hypercholesterolemia (plasma total cholesterol greater-than-or-equal-t o 2.5 g/l) to evaluate the efficacy and safety of simvastatin in hyper cholesterolemia with an inadequate response to a low-fat diet. A low-f at diet was initiated or continued in every case. Lipid-lowering drugs were discontinued six weeks before inclusion into the treatment perio d. 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 pat ients 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 re ductions (P < 0.001) in the levels of total cholesterol (- 23.6%), LDL cholesterol (- 32.8 %), and triglycerides (- 17.2 %), as well as a si gnificant (P < 0.001) 10.1% increase in the level of high-density lipo protein (HDL) cholesterol. After 4 weeks, the simvastatin dosage was i ncreased to 20 mg/day in 47.9% of patients. At the end of the study, 8 2% 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 pat ients and consisted mainly of gastrointestinal complaints (3.7%) and m uscular symptoms (1.5%). Treatment-related laboratory test abnormaliti es were found in 1.3% of patients and consisted of elevations in trans aminase levels (0.5%) or gamma-GT levels (0.1%) and elevations in crea tine phosphokinase levels without concomitant muscular symptoms (0.7%) . Only 1.6% of patients were withdrawn from the drug. These data confi rm the efficacy and favorable clinical and laboratory test safety prof ile of simvastatin in clinical practice.