TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA IN CHILDREN AND ADOLESCENTS - EFFECT OF LOVASTATIN

Objective. Familial hypercholesterolemia (FH), an inherited autosomal dominant disorder of lipoprotein metabolism, is associated with premat ure atherosclerosis. The recommended pediatric therapy consists of die tary intervention and, when necessary, treatment with bile acid-bindin g resins. However, compliance has been poor in many children. Therefor e, our objectives were to determine the efficacy, safety, and toleranc e of the short-term use of lovastatin, a 3-hydroxy 3-methylglutaryl co enzyme A reductase inhibitor, in the control of severe FH in a male pe diatric population and to evaluate the dose-response relationship. Met hods. Sixty-nine male patients with FH 12.9 +/- 2.4 years of age (mean +/- SD) participated in this multicenter, randomized, double-blind tr ial. After a 4-week placebo period, the patients were allocated to fou r treatment groups (lovastatin 10, 20, 30, or 40 mg/d) for 8 weeks. Pl asma lipid and apolipoprotein (Ape) concentrations were measured every 2 weeks. Clinical and laboratory evidence of adverse events was monit ored periodically throughout the study. Results. All lovastatin doses reduced total cholesterol (-17% to -29%), low-density lipoprotein chol esterol (-21% to -36%), and ApoB (-19% to -28%) concentrations. A dose -response relationship was seen, and between-group comparisons showed that results were significantly improved up to a dose of 30 mg/d. We o bserved a 7% increase in high-density lipoprotein cholesterol and a 4% increase in ApoA1 concentrations. The medication was well tolerated b y all patients. No serious clinical adverse experience was reported. L ovastatin increased aspartate aminotransferase concentrations, but the re was no evidence of a dose-response relationship, and no value excee ded two times the upper limit of normal. No significant change in alan ine aminotransferase was observed. Three patients had marked (more tha n three times the upper limit of normal) asymptomatic elevations in th eir creatine kinase values, which returned spontaneously to normal, an d no action was required regarding the drug. Conclusions. Lovastatin i s an effective therapy for severe FH in children and adolescents. It w as well tolerated, and the occurrence of adverse experiences of clinic al significance was very low. Long-term pediatric studies are indicate d.