Efficacy and Safety of Lovastatin in Adolescent Males With Heterozygous Familial Hypercholesterolemia: A Randomized Controlled Trial

• Published in: JAMA : the journal of the American Medical Association 1999-01, Vol.281 (2), p.137-144
• Main Authors: Stein, Evan A, Illingworth, D. Roger, Kwiterovich, Jr, Peter O, Liacouras, Chris A, Siimes, Martti A, Jacobson, Marc S, Brewster, Thomas G, Hopkins, Paul, Davidson, Michael, Graham, Kevin, Arensman, Frederick, Knopp, Robert H, DuJovne, Carlos, Williams, Christine L, Isaacsohn, Jonathan L, Jacobsen, Carol A, Laskarzewski, Peter M, Ames, Sharon, Gormley, Glenn J
• Format: Article
• Language: English
• Subjects: Adolescent; Anticholesteremic Agents - therapeutic use; Apolipoproteins - blood; Biological and medical sciences; Blood Chemical Analysis; Child; Cholesterol; Creatine Kinase - blood; Double-Blind Method; Drug therapy; General and cellular metabolism. Vitamins; Growth - drug effects; Heterozygote; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - drug therapy; Lipids - blood; Lovastatin - therapeutic use; Male; Males; Medical disorders; Medical sciences; Nutritional Status - drug effects; Pharmacology. Drug treatments; Sexual Maturation - drug effects; Teenagers; Transaminases - blood
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.281.2.137

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-3-methylglutaryl 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 MEASURES The primary efficacy outcome measure was low-density lipoprotein cholesterol (LDL-C). Primary safety measures were growth and sexual development. RESULTS Compared with placebo, LDL-C levels of patients receiving lovastatin decreased significantly (P