Familial Hypercholesterolemia Management Flashcards

Ezetimibe lowers LDL-C in FH patients primarily through which mechanism?

Answer: Blocking NPC1L1 transporter in intestinal enterocytes

Ezetimibe inhibits the NPC1L1 transporter at the brush border of intestinal enterocytes, reducing cholesterol absorption by approximately 50%.

Which PCSK9 inhibitor was the first FDA-approved monoclonal antibody for reducing LDL-C in heterozygous FH?

Answer: Alirocumab

Alirocumab (Praluent) was the first PCSK9 inhibitor approved by the FDA in 2015 for heterozygous FH management.

Inclisiran differs from monoclonal antibody PCSK9 inhibitors in that it:

Answer: Uses siRNA to suppress hepatic PCSK9 synthesis, allowing twice-yearly dosing

Inclisiran is an siRNA that silences PCSK9 mRNA in hepatocytes, reducing PCSK9 production and enabling dosing only twice per year after initiation.

Lomitapide is approved for homozygous FH and works by inhibiting which protein?

Answer: Microsomal triglyceride transfer protein (MTP)

Lomitapide inhibits MTP, which is essential for assembling VLDL and chylomicrons, thereby reducing hepatic and intestinal lipoprotein secretion.

Bempedoic acid reduces LDL-C in FH patients by inhibiting ATP citrate lyase. Its key advantage over statins is that it:

Answer: Is activated only in the liver, minimizing muscle-related side effects

Bempedoic acid requires hepatic activation by ACSVL1 and is not converted to its active form in muscle, reducing the risk of myopathy seen with statins.

A patient with HeFH on maximum-dose rosuvastatin plus ezetimibe still has LDL-C of 185 mg/dL. According to ACC/AHA guidelines, what is the most appropriate next step?

Answer: Add a PCSK9 inhibitor

Current guidelines support adding a PCSK9 inhibitor when LDL-C remains above goal despite maximally tolerated statin plus ezetimibe in high-risk FH patients.

Which clinical finding distinguishes xanthelasma from tendon xanthomas in FH patients?

Answer: Xanthelasma are soft yellowish plaques on eyelid skin; tendon xanthomas are firm nodules within tendon tissue

Xanthelasma are soft lipid deposits on periorbital skin with lower FH specificity, while tendon xanthomas are firm cholesterol deposits within tendon fibers highly specific for FH.