Table 2. Lipid-modifying treatment for familial hypercholesterolemia.

Manifestation of heterozygous FH	Manifestation of homozygous FH
Statins*1	Statins*1
Cholesterol resorption inhibitor (ezetimibe)*2	Cholesterol resorptioan inhibitor (ezetimibe)*2
Anion exchanger*3	Anion exchanger*3
	MTP inhibition (lomitapide)*4
LDL apheresis	LDL apheresis
	In selected cases: liver transplant (historically: portocaval shunt)
Undergoing clinical development: PCSK9 inhibitors Apolipoprotein B antisense oligonucleotide	Undergoing clinical development: PCSK9 inhibitors Apolipoprotein B antisense oligonucleotide

^*1Although statins are the first-line therapy for HeFH, HoFH patients have less or no response to this treatment because statins reduce cholesterol by increasing expression of LDL receptors that are absent in HoFH. Guidelines recommend use of the strongest statins at the highest authorized dose tolerated by the patient.

^*2Restriction of enteral resorption of both dietary and biliary cholesterol by using ezetimibe to inhibit an intestinal cholesterol transporter, Niemann-Pick C1-like protein 1 (NPC1L1), increases the LDL-lowering effects of statins. This mechanism of action explains a therapeutic effect beyond that of stain treatment in HoFH (e46, e47).

^*3Anion exchangers lead to lowered LDL cholesterol by inhibiting enterohepatic bile acid circulation. Use is restricted due to relatively poor tolerability, but this can be improved using the newer bile acid sequestrant colesevelam (e22).

^*4Inhibition of synthesis of very-low-density lipoprotein (VLDL), the precursor of low-density lipoprotein (LDL)