Bile acid sequestrants show potential in children with familial hypercholesterolemia

The lipid-lowering efficacy and tolerability of bile acid sequestrants suggest that these agents have potential in pediatric patients with familial hypercholesterolemia (FH), according to a recent literature review from the University of Chicago Pritzker School of Medicine. 

The benefits and risks of pharmacological therapy in this population are limited by the absence of long-term data, wrote review author Michael H. Davidson, MD.   However, because of the high lifetime risk of coronary heart disease associated with FH, the American Academy of Pediatrics’ recommendation to initiate therapy in children aged over 8 years with low-density lipoprotein cholesterol (LDL-C) levels >190 mg/dL appears warranted.

FH occurs most often as a result of a mutation in the low-density lipoprotein receptor gene.  It is inherited in an autosomal-codominant pattern and is characterized by elevated levels of LDL-C, regardless of diet and lifestyle, and the development of cutaneous xanthomas and coronary atherosclerosis. Children with FH show altered endothelial function, a feature closely linked with cardiovascular risk in adulthood.

The author identified 5 studies that evaluated bile acid sequestrant therapy in children aged <18 years with FH, including 2 studies with colestipol, 2 with cholestyramine, and 1 colesevelam.  Two additional studies were identified that combined bile sequestrants with low-dose statins.

Although these agents alone, or in combination with a statin, were efficacious in reducing lipid levels, their use in children with FH remains controversial because of insufficient data and concerns regarding safety and cost effectiveness.  The author noted that the effect of lipid-lowering therapies on reducing the incidence of cardiovascular events is not yet established, nor is there consensus on the age for initiation of therapy.  In addition, adherence to therapy and tolerability remain challenging issues in the pediatric population. 

Studies suggest that restricting dietary fat in children may lead to inadequate energy supplies and subsequent impaired growth and development.  This prompted concerns that lipid-lowering therapy may affect growth.  However, studies of bile acid sequestrants show growth retardation does not occur during pharmacological treatment of FH.

Currently, colesevelam is the only bile acid sequestrant approved for use in the United States in children with heterozygous FH.  However, it has not been studied in children aged <10 years or in premenarchal girls.