ICD-10 Specific code E78.01: Homozygous familial hypercholesterolemia

Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase. Atorvastatin lowers plasma cholesterol and lipoprotein serum concentrations by inhibiting HMG-CoA reductase and subsequently cholesterol biosynthesis in the liver and increases the number of hepatic LDL receptors on the cell surface for enhanced uptake and catabolism of LDL.

Evinacumab is a recombinant human monoclonal antibody, which specifically binds to and inhibits ANGPTL3. ANGPTL3 is a member of the angiopoietin-like protein family that is expressed primarily in the liver and plays a role in the regulation of lipid metabolism by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL). Evinacumab blockade of ANGPTL3 lowers TG and HDL-C by releasing LPL and EL activities from ANGPTL3 inhibition, respectively.

Evolocumab binds selectively to PCSK9 and prevents circulating PCSK9 from binding to the low density lipoprotein receptor (LDLR) on the liver cell surface, thus preventing PCSK9-mediated LDLR degradation. Increasing liver LDLR levels results in associated reductions in serum LDL-cholesterol (LDL-C).

Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase. Rosuvastatin increases the number of hepatic LDL receptors on the cell-surface, enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of VLDL, thereby reducing the total number of VLDL and LDL particles.

Simvastatin has a potent activity in inhibiting HMG-CoA reductase (3-hydroxy–3-ethylglutaryl-CoA-reductase). Simvastatin has been shown to reduce both normal and elevated LDL-C concentrations.

Plasma cholesterol is derived from intestinal absorption and endogenous synthesis. Ezetimibe and simvastatin are two lipid-lowering compounds with complementary mechanisms of action. Ezetimibe/simvastatin combination reduces elevated total cholesterol (total-C), LDL-C, apolipoprotein B (Apo B), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C), and increases high-density lipoprotein cholesterol (HDL-C) through dual inhibition of cholesterol absorption and synthesis.