Which of the following statements regarding FH is NOT true?
A. The Food and Drug Administration (FDA) indications for LDL apheresis after maximal tolerated pharmacologic therapy include (a) homozygous FH patients and (b) heterozygous FH in the absence of CHD when LDLC ≥300 mg/dL and in the presence of CHD when LDL-C ≥200 mg/dLLomitapide has been approved to treat homozygous and heterozygous FH. Homozygous FH occurs in 1 in 1 million individuals. TC levels are generally >600 mg/dL, with LDL-C levels six- to eightfold higher than average. Without treatment, death from MI occurs in the first or second decades of life. In addition to the xanthomas observed in heterozygotes, FH homozygotes are commonly affected by interdigital xanthomas; tuberous xanthomas on the hands, elbows, buttocks, and feet; and planar xanthomas on the posterior thighs, buttocks, and knees. The mainstay of therapy for FH homozygotes is LDL apheresis and has been associated with stabilization or regression of atherosclerotic lesions and improvement in symptoms. Since immediate reductions in LDL-C of 50% to 80% rebound quickly, the process is performed every 2 to 4 weeks to keep intrapheresis LDL-C ≤120 mg/dL.
Both mipomersen and lomitapide were FDA approved in 2013 as orphan drugs for management of patients with homozygous FH only. Mipomersen is a subcutaneously injectable RNA antisense oligonucleotide. Lomitapide blocks microsomal TG transport protein (a key protein in assembly and secretion of apoB-containing lipoproteins in the liver and intestines) reducing hepatic secretion of VLDL. These therapies have a small target population, require risk evaluation and mitigation strategy limiting use to specialized centers, and have concerns with liver toxicity and hepatic steatosis due to accumulation of TGs not secreted into VLDL.
Several clinical diagnostic criteria for FH exist, with the 15-year Simon Broome Register Group being the most commonly used. Definite FH is as defined above. Possible FH by this criteria is defined as (a) above PLUS and (b) MI before age 50 in second-degree relative, or before 60 in first-degree relative or elevated cholesterol in first-degree relative, or >290 mg/dL in second-degree relative.