Grant: Homozygous Familial Hypercholesterolemia: Prevention of Aggressive Atherosclerosis Requires Aggressive Diagnosis and Treatment

Video Transcription

Video Summary

This webinar, part of the ACE Rare Diseases and Hormone Disorders series, focused on homozygous familial hypercholesterolemia (HoFH), a rare but aggressive genetic disorder causing extremely high LDL cholesterol levels (often >400 mg/dL) and premature cardiovascular disease. Dr. Lance Sloan introduced the pathophysiology, highlighting mutations mainly in the LDL receptor gene and others affecting cholesterol metabolism. HoFH leads to early atherosclerosis, cardiac events in childhood or adolescence, and shortened lifespan (average death at 32 years). Despite its severity, diagnosis remains low, especially in the U.S.<br /><br />Dr. Elliot Brenton discussed treatment challenges and approaches. Standard LDL-lowering therapies like statins, ezetimibe, and PCSK9 inhibitors have limited effect in HoFH due to LDL receptor defects, though PCSK9 inhibitors may help milder cases. Intensive therapies independent of the LDL receptor are crucial: lipoprotein apheresis, which physically removes LDL and significantly reduces cardiovascular events; lomitapide, an oral agent that blocks VLDL assembly but requires careful liver monitoring due to fat accumulation; and evinacumab, a newer injectable that inhibits angiopoietin-like 3 protein, reducing LDL through alternative pathways.<br /><br />For many patients, combination therapy is necessary to reach LDL goals (<55-70 mg/dL per European guidelines). Early screening, particularly in children, is essential to initiate timely treatment due to the risk of early cardiovascular events. Special populations, including children and pregnant women, can benefit from these therapies, with apheresis being especially safe in pregnancy. The experts emphasized aggressive diagnosis and treatment to improve survival and reduce cardiovascular events in this high-risk population.

Keywords

homozygous familial hypercholesterolemia

HoFH

LDL cholesterol

genetic disorder

cardiovascular disease

LDL receptor mutation

lipoprotein apheresis

lomitapide

evinacumab

early screening