The effects of simvastatin on serum lipoproteins in severe hypercholesterolaemia.

The effects of simvastatin, an inhibitor of cholesterol synthesis, on serum lipids, lipoprotein composition and apolipoproteins were evaluated in a total of 50 patients with hypercholesterolaemia. In the first study, 24 patients (mean serum cholesterol 10.74 +/- 1.59 mmol/l) were treated with simvastatin 40 mg daily for 24 wk. Serum cholesterol and low density lipoprotein (LDL) cholesterol decreased to average values 29-36% and 35-42% below the basal value, respectively. Serum triglycerides decreased by 16-28%, and high density lipoprotein (HDL) cholesterol increased by 6-11%. Apolipoprotein A-I concentration increased 6-8% and that of apolipoprotein B decreased 29-33%. The composition of LDL remained unchanged whereas the very low density lipoproteins became enriched in triglycerides. Lipoprotein Lp(a) was not affected. In the second study 26 patients (mean serum cholesterol 12.35 +/- 2.05 mmol/l) were treated with simvastatin 40 mg daily as monotherapy or combined with a bile acid binding resin for 2 yr. Serum cholesterol levels decreased to values which remained stable throughout the entire study period; after 2 yr this decrease amounted to 43%. Compared to monotherapy, combination therapy yielded a further 12% decrease of cholesterol. In the entire group, triglycerides decreased by 16% and HDL cholesterol increased by 9%. Side effects were limited to slight increases in alanine aminotransferase and creatine phosphokinase in some patients. Simvastatin appears to be an important asset in the treatment of hypercholesterolaemia.