Efficacy and Safety of Lovastatin in Adolescent Males With Heterozygous Familial Hypercholesterolemia
Authors: Evan A. Stein, D. Roger Illingworth, Peter O. Kwiterovich, Jr, Chris A. Liacouras, Martti A. Siimes, Marc S. Jacobson, Thomas G. Brewster, Paul Hopkins, Michael Davidson, Kevin Graham, Frederick Arensman, Robert H. Knopp, Carlos DuJovne, Christine L. Williams, Jonathan L. Isaacsohn, Carol A. Jacobsen, Peter M. Laskarzewski, Sharon Ames, Glenn J. Gormley
Journal: JAMA (1999)

HYPERCHOLESTEROLEMIA(FH) is a dominant genetic disorder first described by Muller 1 nearly 60 years ago.The elevated circulating low-density lipoprotein cholesterol (LDL-C) levels found in FH are caused by a defect in receptor-mediated LDL clearance 2 and are the underlying cause of the marked increase in early coronary artery disease (CAD). 3In men with untreated heterozygous FH (HeFH), the risk of clinically overt CAD is approximately 5% by age 30 years, 20% by age 40 years, and 50% by age 50 years. 3,4Only about 15% of men with HeFH reach age Context Heterozygous familial hypercholesterolemia (HeFH) is a common disorder associated with early coronary artery disease, especially in men.The age at which drug therapy should be started is still controversial, as is the use of 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitors (statins).Objective To assess the lipid-lowering efficacy, biochemical safety, and effect on growth and sexual development of lovastatin in adolescent boys with HeFH.Design One-year, double-blind, placebo-controlled, balanced, 2-period, 2-arm randomized trial.In the first period (24 weeks), lovastatin was increased 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 Finland.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 intervention, 49 placebo) completed the first and second periods, respectively.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 MeasuresThe primary efficacy outcome measure was lowdensity lipoprotein cholesterol (LDL-C).Primary safety measures were growth and sexual development. ResultsCompared with placebo, LDL-C levels of patients receiving lovastatin decreased significantly (PϽ.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 testicular volume were not significantly different between the lovastatin and 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 parameters.Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C, the major carrier of vitamin E in the circulation. ConclusionsThis study in adolescent boys with HeFH confirmed the LDL-Creducing effectiveness of lovastatin.Comprehensive clinical and biochemical data on growth, hormonal, and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks, although further study is required.