Simvastatin in the effective reduction of plasma lipoprotein levels in familial dysbetalipoproteinemia (type III hyperlipoproteinemia)

Abstract

Purpose: Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is characterized by an increase of serum lipids caused by an accumulation of remnant particles of triglyceride-rich lipoproteins. We studied the efficacy of simvastatin, an inhibitor of the biosynthesis of cholesterol, in this disorder.

Patients and methods: Twelve patients participated in an open-label study. After a three-week placebo period, they were treated with increasing doses (10 mg twice a day, 20 mg twice a day, and 40 mg twice a day) of simvastatin in six-week periods.

Results: With the 80-mg dose, the mean serum cholesterol level decreased from 12.30 +/- 4.96 to 5.29 +/- 1.24 mmol/L (mean reduction, 54%) and the mean serum triglyceride level decreased from 8.77 +/- 7.16 to 3.61 +/- 1.33 mmol/L (-48%); this was due to a decrease in very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) lipids. There was a decrease in the ratio of VLDL cholesterol to serum triglycerides and in the apolipoproteins B and E, suggesting a reduction in the amount of circulating atherogenic remnant particles. Except for a slight increase in serum alanine aminotransferase levels in three patients, no side effects were observed.

Conclusion: These data show that levels of serum lipids can be effectively reduced by simvastatin in familial dysbetalipoproteinemia.