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
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.