Advanced therapy in familial hypercholesterolemia

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.