University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• 35 y/o male presented with chest pain, found to have LAD occlusion and stent was placed. His 12 y/o son was found to have an LDL of 225. Are HMG Co-A reductase inhibitors efficacious and safe for his son?

Clinical Bottom Lines

1. Heterozygous familial hypercholesterolemia is most common cause of elevated cholesterol in children in the U.S. and is caused by a defect in the receptor-mediated clearance of LDL. It is associated with accelerated atherosclerosis and early mortality due to coronary events.¹
2. Need to selectively screen children with parents or grandparents found to have premature CVD (MI, angina pectoris, CVA, PVD, or sudden cardiac death) at age <55 with a lipid panel. Children with parents that have total cholesterol >240, should be screened with a total cholesterol level.^2,3
3. HMG CO-A reductase inhibitor Lovastatin is effective in decreasing LDL cholesterol in children >10 y/o by 25% when diet therapy alone has failed.¹
4. Data do not suggest any adverse effects on normal growth and development in male adolescents but formal evaluations have not been done in females. Larger studies are needed to show safety.¹
5. There is no evidence that primary prevention in childhood or adolescence with drug therapy to reduce LDL leads to decreased mortality or morbidity in adulthood.

Summary of Key Evidence

1. 132 boys aged 10-17 years with heterozygous familial hypercholesterolemia were randomized to placebo vs. treatment with Lovastatin in a 48 week, double-blind, placebo-controlled study. In the first 24 weeks, Lovastatin was increased from 10mg/d to 20mg/d and 40mg/d at 8 and 16 weeks respectively vs. placebo. During the second 24 weeks, Lovastatin was kept at 40mg/d vs. placebo.
2. Patients were monitored for lipid levels, hepatic enzymes, CK, growth, sexual maturation, nutritional levels, thyroid, adrenal, and pituitary function.
3. For efficacy analysis, patients needed to complete the 8 week phases to be included in the summary statistics. For safety, analysis was carried out on an intent-to-treat basis. Study was not powered to detect significant difference in safety.
4. Lovastatin reduced LDL by 17-27%, Tot Chol by 13-21% at all dosages. There was a minimal and non-significant increase in HDL.
5. Clinical and biochemical data on growth, hormones, and nutrition indicate no significant difference between placebo and Lovastatin over 48 weeks. (Further studies are required).

Additional Comments

• Elevated cholesterol levels in children may not meet adult levels that qualify for treatment, therefore universal screening is not recommended.
• This study had limited ability to detect adverse events, was not powered to detect significant difference in safety, and no adolescent females were included.
• The recommended first line drugs for treatment of hypercholesterolemia in children >10 y/o is Bile Acid sequestrants. There are no good studies for long-term safety in children and have not been evaluated in placebo-controlled trials in children. They have poor compliance due to GI side effects and cause decreased absorption of vitamins. Only decrease LDL by 17-19%.
• Niacin is recommended for use after bile acid sequestrants, even though there are no good long term safety trials and are poorly tolerated. Cause glucose intolerance in diabetics. Need to take an aspirin before to avoid associated flushing.
• Cost is similar for HMG CO-A reductase inhibitors and bile acid sequestrants, niacin is less expensive based on 30 day treatment. Lovastatin ($41-261), Cholestyramine ($48-170), Niacin ($25-76).

Citation

1. Stein EA, et al. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: A randomized controlled trial. JAMA 1999; 281: 137-144.
2. American Academy of Pediatrics Committee on Nutrition. Cholesterol in childhood. Pediatrics 1998; 101: 141-147.
3. National Cholesterol Education Program. Report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 1992; 89:525-84.

CAT Author: Shadi Imani Miller, MD

CAT Appraisers: John G. Frohna, MD

Date appraised: March 26, 2001