Advanced therapy in familial hypercholesterolemia.

QUESTION: A 9-year-old child with elevated low-density lipoprotein cholesterol (LDL-C) levels was diagnosed with familial hypercholesterolemia (FH) and received high-intensity statin therapy, but their LDL-C levels are still elevated. What are the current recommendations for early diagnosis and treatment of FH to reduce the risk of early-onset atherosclerosis and improve long-term cardiovascular outcomes, and how safe and effective are these therapies for pediatric patients?

ANSWER: FH is a complex genetic disorder causing highly elevated levels of LDL-C and risk of cardiovascular disease. Any child with homozygous FH should be referred to a specialist for consultation. Monoclonal antibodies are recommended by guidelines as adjunct treatments for FH when statins are insufficient. They have been studied as treatment for adults with FH, but direct evidence for pediatric patients is limited. Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and angiopoietin-like protein 3 (ANGPTL3) inhibitors can provide meaningful reductions in LDL-C levels when conventional therapies alone, including statins and ezetimibe, are inadequate. Evolocumab, a PCSK9 inhibitor, has demonstrated safety and efficacy in adult patients with heterozygous FH and a moderate effect in children with homozygous FH. Evinacumab, an ANGPTL3 inhibitor, has shown greater efficacy than evolocumab for treating homozygous FH in limited pediatric studies. Longer-term and larger-scale research on evolocumab and evinacumab use in children will help elucidate long-term effects.