The aim of this study was to investigate the safety and long-term effects on serum
lipid levels of low-dose
simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl
coenzyme A reductase, in Japanese patients with moderate primary
hypercholesterolemia. We assigned 201 patients (68 men and 133 women; mean +/- SD age, 61.3 +/- 10.2 years) with serum total
cholesterol levels > or = 220 mg/dL to receive
simvastatin 5 mg each evening; the treatment period was 1 year. Serum total
cholesterol,
triglycerides, and
low-density lipoprotein (
LDL) cholesterol levels decreased significantly in response to
simvastatin therapy, and the changes were maintained throughout the treatment period. Mean total
cholesterol decreased from 269.9 +/- 35.4 mg/dL to 215.2 +/- 34.5 mg/dL (20.3%),
triglycerides decreased from 183.0 +/- 110.2 mg/dL to 155.5 +/- 88.5 mg/dL (15.0%), and
LDL cholesterol decreased from 180.0 +/- 33.1 mg/dL to 130.1 +/- 35.1 mg/dL (27.7%). Total
cholesterol,
triglycerides, and
LDL cholesterol tended to decline when the pretreatment values were higher; the critical values and the bidirectional changes of the serum
lipid levels were 188.1, 109.5, and 91.6 mg/dL, respectively. Although the serum level of
high-density lipoprotein cholesterol did not change significantly, it tended to increase more when the pretreatment values were lower; the "critical value" was 70 mg/dL. Nine patients experienced mild adverse events, but none discontinued
simvastatin during the 12-month treatment period. We found that low-dose
simvastatin therapy is effective in achieving long-term decreases in serum
lipid levels and is well tolerated by patients with moderate
hypercholesterolemia.
Simvastatin therapy may result in normalization of serum
lipid levels.