Homozygous familial hypercholesterolaemia (
HoFH) is a rare, life-threatening disease characterised by highly elevated
low-density lipoprotein cholesterol levels (
LDL-C), cutaneous and tendinous xanthomata, severe and precocious
atherosclerosis, and aortic and supra
aortic valve disease. Although treatment with
apheresis and
lipid-lowering drugs has improved event-free survival of
HoFH patients, the condition is still associated with early onset
cardiovascular disease and death due to residual
high cholesterol levels. Hydroxy-3-methylglutaryl-coenzyme A (
HMG-CoA) reductase inhibitors or
statins are powerful
cholesterol-lowering agents, but
HoFH patients are often inadequately controlled on
statins alone; therefore, a variety of other medications, including the
cholesterol absorption inhibitor
ezetimibe,
bile acid sequestrants and
niacin, have been used to try to achieve recommended
LDL-C goals. However, even in patients with access to the best available treatments,
HoFH has continued to be associated with extreme rates of morbidity and premature mortality. The
microsomal triglyceride transfer protein inhibitor
lomitapide has recently received regulatory approval in the European Union and the United States of America for use in patients with
HoFH and a number of other agents are currently in development, including
apolipoprotein B
antisense oligonucleotides (approved in the US), and
proprotein convertase subtilisin kexin type 9 (PCSK-9) inhibitors. These new approaches may result in improved clinical outcomes for
HoFH patients. In the future it will be important to begin treatment early and to treat as aggressively as possible.