Prediction of the therapeutic response to simvastatin by pretreatment lipid concentrations in 2082 subjects

2082 hypercholesterolemic subjects were treated with simvastatin for 12 weeks. In 530 patients the dose was increased after 6 weeks from 10 to 20 mg because of persistently high cholesterol concentrations. Total cholesterol (TC) in the 1552 patients taking 10 mg fell by 1.61 mmol.l-1 (18.4%), LDL cholesterol (LDLC) by 1.53 mmol.l-1 (25.2%), and triglycerides (TG) by 0.13 mmol.l-1 (5.5%); HDL cholesterol (HDLC) significantly increased by 0.05 mmol.l-1 (3.6%). In the 530 patients taking 20 mg TC fell by 1.89 mmol.l-1 (19.9%), LDLC by 1.78 mmol.l-1 (26.0%), and TG by 0.13 mmol.l-1 (5.5%); HDLC increased by 0.05 mmol.l-1 (3.7%). The reductions in TC, LDLC, and TG were positively correlated and the increase in HDLC negatively correlated with their respective baseline values. There were independent significant correlations of the fall in LDLC with sex (MANOVA), baseline TG, and adherence to a lipid-lowering diet. The falls in TG significantly correlated with baseline fructosamine concentrations and dietary adherence. There were 571 adverse events in 16.6% of the patients but no case of myopathy. These results show that simvastatin is usually well tolerated and that its effects on TC and LDLC depend on their baseline concentrations.