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What about effective therapies for FH? Here ideally the focus should be on interventions that up-regulate the LDL receptor, starting with dietary interventions. A low cholesterol diet will reduce serum LDL-C levels in heterozygotes by 10-25%, but in homozygotes by <10%. Statins up-regulate the LDL receptor via inhibition of HMG coenzyme-A reductase and result in >25% reduction in LDL-C in heterozygote patients but <10% reduction in homozygotes because of either the lack of LDL receptors or the dysfunction of those receptors.
Bile acid resins also up-regulate the LDL receptor, with again a reduction of 10-25% in heterozygous FH, but of <10% in homozygotes. The cholesterol absorption inhibitor ezetimibe decreases cholesterol absorption and increases activity of the LDL receptor, with again a reduction of 10-25% in heterozygous FH, but of <10% in homozygotes. Plant stanol esters also increase the LDL receptor activity showing a reduction of 10-25% in heterozygous FH, but of <10% in homozygotes.
Nicotinic acid (niacin) does not up-regulate the LDL receptor, and therefore it is probably a fourth-line intervention from a pharmacologic standpoint in patients with FH. Niacin does decrease VLDL synthesis, thus leading to decreased production of LDL and resulting in sometimes >25% reduction in LDL cholesterol in heterozygous FH patients, with a 10% reduction in homozygote patients.
[34] Rader DJ, et al. J Clin Invest. 2003;111:1795-1803.