New treatments on the horizon for familial hypercholesterolemia.

Patients with familial hypercholesterolemia (FH) have higher baseline LDL cholesterol (LDLc) levels and are at high risk of developing premature cardiovascular disease. Disease is attributed to mutations in the LDLR gene, which encodes the LDL receptor protein and whose deficiency results in decreased uptake of apoB-containing cholesterol particles by the liver and elevated serum LDLc levels. Heterozygous FH is inherited in an autosomal-dominant pattern and has an incidence of 1:500 in the general population. These patients usually present with premature cardiovascular disease at 30-40 years of age and have baseline LDLc levels ranging from 190 to 230 mg/dl. Homozygous FH, however, is much rarer, occurring in one in a million births; those afflicted present with severe cardiovascular disease in childhood and have baseline LDLc levels greater than 300 mg/dl. Often FH patients do not reach their target LDLc levels on conventional therapies such as statins. Even with combination therapy, the percent of FH patients reaching target cholesterol levels is less than 30% and while apheresis is a therapeutic option for those with the most severe disease, many FH patients seek less invasive therapeutic strategies. New classes of cholesterol medications, aimed at either lowering LDLc levels or altering the progression of intra-arterial plaque, are currently in clinical development and may offer alternative or adjunctive therapies for this high-risk population.