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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Multimodal Treatment of Homozygous Familial Hypercholesterolemia

Author(s): Thomas Gossios*, Ioanna Zografou, Veta Simoulidou, Athina Pirpassopoulou, Konstantinos Christou and Asterios Karagiannis

Volume 24 , Issue 31 , 2018

Page: [3616 - 3621] Pages: 6

DOI: 10.2174/1381612824666181009095522

Price: $65


Background: Familial Hypercholesterolemia (FH) is an autosomal-dominant genetic disease, associated with premature atherosclerotic Cardiovascular Disease (CVD), especially in its homozygous type (HoFH).

Objective: The aim of this review is to discuss the safety and efficacy of combination treatments (procedures and drugs) for HoFH.

Results: Historically, liver transplantation was used first; however, it is currently considered only as a last resort for some patients. In the mid 70’s, LDL aphaeresis was introduced and remains up today the treatment of choice for patients of any age, despite its significant cost. The use of Ezetimibe results in additive 15-20% reductions in LDL-C regardless of the therapeutic approach, while statins are modestly effective in patients with class 4 or 5 mutations, in which LDL Receptors (LDLR) are present. One of the novel drugs for HoFH is Lomitapide, which is a highly effective oral agent, but is also exceedingly expensive ($350, 000/year). Mipomersen is administered every week subcutaneously, is also effective but has been approved only in the US mainly due to injection site reactions up to 80%. Both Lomitapide (mainly) and Mipomersen have been found to promote fat accumulation in the liver, resulting in subsequent serum transaminases elevations. PCSK9 inhibitors are effective in those with partial LDLR presence and function by reducing frequency of LDL apheresis, improve cost effectiveness of treatment.

Conclusion: Pediatric and adult HoFH treatment needs combination of procedures and drugs. The main treatment is LDL-C apheresis aided by ezetimibe and PCSK9 inhibitors. Lomitapide needs caution, and liver transplantation is an alternative as the last resort.

Keywords: Homozygous familial hypercholesterolemia, LDL-C, liver transplantation, LDL apheresis, ezetimibe, statins, lomitapide, mipomersen, PCSK9 inhibitors.

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