Long-term treatment of severe familial hypercholesterolemia in children: effect of sitosterol and bezafibrate.

Seven prepubertal children (age range 5.3 to 10.8 years) with severe heterozygous familial hypercholesterolemia (serum cholesterol concentration 416 +/- 85 mg/dL and low-density lipoprotein [LDL] cholesterol concentration 360 +/- 90 mg/dL) were first treated by dietary intervention, second by sitosterol (3 x 2 g/d), and third by bezafibrate (2 x 200 mg/d). Each treatment period lasted 3 months. Subsequently, a treatment combining half the dose of sitosterol and bezafibrate was administered for the following 24 months. Diet alone reduced total and LDL cholesterol values by 4.5% (not significant) and 6.6% (P less than .05), respectively. Sitosterol lowered total and LDL cholesterol values by 17% (P less than .05) when compared with diet alone. Compared with sitosterol, bezafibrate produced a more pronounced effect on total and LDL cholesterol values (-18% and -28%, P less than .05), and high-density lipoprotein cholesterol concentration increased significantly from 48 mg/dL to 55 mg/dL. Combined treatment with half the dose each of sitosterol and bezafibrate was as effective as the higher dose of bezafibrate, and reduction averaged almost 40% and 50% for total and LDL cholesterol values; this lipid-lowering effect persisted for the next 24 months. Laboratory safety parameters and physical examination revealed no obvious side effects. This study indicates that the combination of sitosterol (3 x 1 g/d) plus bezafibrate (1 x 200 mg/d) is an alternate, acceptable, safe, and effective therapeutic approach for treatment of severe hypercholesterolemia in children with high-risk familial hypercholesterolemia.