Table 7d.

Treatment of Manifestations in Children and Adults with Severe Familial Hypercholesterolemia (HoFH)

Manifestation/ConcernTreatmentConsiderations/Other
Hyperlipidemia
  • Referral to lipid specialist w/expertise in FH
  • Multi-drug therapy usually required (See Table 7b.)
Evolocumab, alicrocumab (PCSK9 inhibitors)
  • 40% mean reduction in LDL-C compared w/placebo; however, persons w/biallelic loss-of-function variants saw no response. 1
  • To date, only evolocumab has been approved for children w/FH & HoFH. 2
In those w/some residual LDLR activity:
  • High-dose statins
  • Ezetimibe
  • Bile acid-binding resins
Medications that target the LDLR may be ineffective in persons w/biallelic loss-of function LDLR pathogenic variants.
LomitapideEffective even w/complete loss of LDLR function; though not formally FDA approved for children, should strongly be considered.
Evinacumab (ANGPTL3 inhibitor) 3
  • Recombinant human monoclonal antibody that binds to & inhibits ANGPTL3
  • Available for adults & children ≥12 yrs w/HoFH
  • Used in conjunction w/other lipid-lowering therapies
LDL apheresis (≤2x/wk) is often required from a young age.Apheresis can ↓ LDL-C levels by 80% acutely & 30% chronically (weekly or biweekly). Apheresis is offered at a limited number (~40-50) of centers in the US.
Liver transplantationUsed in rare cases in some centers 4
Atherosclerotic CVD Severe FH can lead to clinical manifestations of atherosclerosis (incl myocardial infarction) in childhood. Children & adults w/clinical atherosclerotic CVD should be evaluated & treated by cardiovascular specialists.

CVD = cardiovascular disease; FH = familial hypercholesterolemia; LDL-C = low-density lipoprotein cholesterol; LDLR = low-density lipoprotein receptor

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From: Familial Hypercholesterolemia

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