Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia - A randomized controlled trial

Context Heterozygous familial hypercholesterolemia (HeFH) is a common disor der associated with early coronary artery disease, especially in men. The a ge at which drug therapy should be started is still controversial, as is th e use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statin s). Objective To assess the lipid-lowering efficacy, biochemical safety, and ef fect on growth and sexual development of lovastatin in adolescent boys with HeFH. Design One-year, double-blind, placebo-controlled, balanced, 2-period, 2-ar m randomized trial. In the first period (24 weeks), lovastatin was increase d at 8 and 16 weeks and the dosage remained stable during the second period (24 weeks). The study was conducted between 1990 and 1994. Setting Fourteen pediatric outpatient clinics in the United States and Finl and. Patients Boys aged 10 to 17 years with HeFH. Of 132 randomized subjects (67 intervention, 65 placebo), 122 (63 intervention, 59 placebo) and 110 (61 i ntervention, 49 placebo) completed the first and second periods, respective ly. Intervention Lovastatin, starting at 10 mg/d, with a forced titration at 8 and 16 weeks to 20 and 40 mg/d, respectively, or placebo. Main Outcome Measures The primary efficacy outcome measure was low-density lipoprotein cholesterol (LDL-C). Primary safety measures were growth and se xual development. Results Compared with placebo, LDL-C levels of patients receiving lovastati n decreased significantly (P < .001) by 17%, 24%, and 27% receiving dosages of 10, 20, and 40 mg/d, respectively, and remained 25% lower than baseline at 48 weeks. Growth and sexual maturation assessed by Tanner staging and t esticular volume were not significantly different between the lovastatin an d placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum hormone levels or biochemical parameters of nutrition. However, the study was underpowered to detect significant differences in safety paramete rs. Serum vitamin E levels were reduced with lovastatin treatment consisten t with reductions in LDL-C, the major carrier of vitamin E in the circulati on. Conclusions This study in adolescent boys with HeFH confirmed the LDL-C-red ucing effectiveness of lovastatin. Comprehensive clinical and biochemical d ata on growth, hormonal, and nutritional status indicated no significant di fferences between lovastatin and placebo over 48 weeks, although further st udy is required.