Fig. 1Low density lipoprotein cholesterol (LDL-C) burden in individuals with or without familial hypercholesterolemia (FH) as function of the onset of statin therapy. Adapted from Nordestgaard et al. [7], with permission from Oxford University Press. CHD, coronary heart disease; HDL-C, high density lipoprotein cholesterol.
Table 1Characteristics of Four Clinical Diagnostic Criteria
|
Simon Broome |
Dutch |
MEDPED |
Japanese |
Process of diagnosis |
Mutation or cholesterol plus xanthoma or family history |
Sum of score for each item |
Cholesterol level alone |
Any two of cholesterol, xanthoma, or family history |
Items |
Total cholesterol >290 or LDL-C >190 mg/dL; xanthoma; mutation; family history of MI or hypercholesterolemia |
Family history of CAD or hypercholesterolemia; history of CAD, cerebral or peripheral vascular disease; xanthoma or corneal arcus; LDL-C ≥150–330 mg/dL |
Total cholesterol ≥290–360 or LDL-C ≥220–260 mg/dL |
LDL-C ≥180 mg/dL; xanthoma; family history of hypercholesterolemia or CAD |
Table 2New Therapeutics Approved for Familial Hypercholesterolemia
|
Lomitapide |
Mipomersen |
PCSK9 inhibitors (evolocumab, alirocumab) |
Action mechanism |
Inhibition of microsomal TG transfer protein; reduction of VLDL synthesis |
Antisense oligonucleotide that binds to mRNA and blocks apoB translation |
Binds to plasma PCSK9, reduces endosomal degradation of LDLR |
Efficacy |
Lowers LDL-C & apoB by 40%–50% on top of ongoing therapy |
Lowers LDL-C & apoB by 20%–30% and lp(a) by 20%–25% on top of ongoing therapy |
Lowers LDL-C by 50%–60%, apoB by 40%–50%, and lp(a) by 20%–30%; 50% reduction of cardiovascular events in preliminary data |
Safety |
GI disturbance (>90%), liver enzyme elevation (14%–34%), and hepatic steatosis |
Injection-site reaction (>75%), influenza-like symptoms (30%–65%), liver enzyme elevation (12%–15%), and hepatic steatosis |
Largely well tolerated; slight injection-site reactions, neurocognitive and muscle-related symptoms |
Remarks |
Approved in USA for hoFH |
Approved in USA, Canada, and Europe for hoFH |
Approved in USA and Europe for FH |