Pharmacologic intervention should be considered for patients 8 years of age and older with LDL > 190 (or > 160 with positive family history or 2 additional risk factors) (or > 130 for patients with personal history of diabetes) (Daniels, 2007).
For patients with LDL > 190 (or >160 with positive family history or personal risk factors of obesity, hypertension, or cigarette smoking), pharmacologic treatment is initiated after a trial of diet therapy
In addition, patients younger than 8 years may be started on oral medications if they have a dramatic increase in LDL concentration (>500 mg/dL) as seen with familial hypercholesterolemia (homozygous form).
The goal of therapy is still undetermined, but should be at least LDL level <160 without other risk factors (or <130 with strong family history, personal history of obesity, diabetes, metabolic syndrome, or other high risk situations such as diseases that predispose to early CVD such as chronic kidney disease, history of congenital heart disease, history of Kawasaki disease).
There are a number of different medications available for treatment of dyslipidemia, although not all are approved for use in children and adolescents.
Bile Acid-Binding Resins (cholestyramine)
Mechanism of action: bind cholesterol in bile acids within the intestinal lumen, preventing reuptake into the enterohepatic circulation
Advantage: No systemic side effects
Result: average lowering of cholesterol 10-20% below baseline
Side effects: GI discomfort - usually enough to prevent their use in younger patients
Availability - granular powder mixed with liquid or a large tablet than cannot be broken
Mechanism of action: decreasing hepatic production of VLDL
Advantage: lower LDL and triglyceride concentrations while increasing HDL concentration
Side effects: flushing, hepatic failure, myopathy, glucose intolerance, hyperuricemia
Adverse effects occur in up to 76% of children (mostly flushing), so this is not recommended for routine use in pediatrics
Availability: slow release tablets and capsules, cannot be chewed or crushed
3-Hydroxy-3-methyl-glutaryl Coenzyme A reductase Inhibitors (statins)
Mechanism of action: inhibit the rate-limiting enzyme for endogenous synthesis of cholesterol
Advantage: lowers intracellular cholesterol level thus upregulating LDL receptors and increasing LDL clearance from the circulation
Result: 20-50% lowering of cholesterol below baseline
Adverse effects: increased hepatic transaminase levels, increased creatine kinase, rhabdomyolysis (rare), teratogenic
Requires monitoring of liver transaminase and creatine kinase levels
There are have been some short term studies conducted in children that show statins are effective and safe
Pravastatin is approved for use in children with familial hypercholesterolemia who are 8 years and older.
Cholesterol-Absorption Inhibitors (ezetimibe)
Mechanism of action: inhibit intestinal absorption of cholesterol, but are also absorbed into the enterohepatic circulation and may exert systemic effects
Advantage: reduction of LDL concentrations by 20%
Adverse effects: GI discomfort
Availability: small tablet
Relatively new medication, but may represent another class of lipid lowering medication that can be effective and safe in children
Mechanism of action: inhibit the synthesis and increase clearance of VLDL apoprotein B leading to decreased VLDL production
Advantage: inhibit peripheral lipolysis and decrease hepatic extraction of free fatty acids leading to decreased hepatic triglyceride production and decreased triglyceride levels
Adverse effects: elevated liver transaminases, elevated creatinine kinase, rhabdomyolysis (especially when used in conjunction with statins)