Novel Lipid-Lowering Therapies Flashcards

Inclisiran is a small interfering RNA (siRNA) therapy that targets PCSK9. What is its primary mechanism of action?

Answer: Degrades PCSK9 mRNA in hepatocytes to reduce PCSK9 synthesis

Inclisiran uses siRNA to degrade PCSK9 mRNA within hepatocytes, thereby reducing PCSK9 protein synthesis and increasing LDL receptor recycling.

A patient on inclisiran 284 mg subcutaneous injection experiences LDL-C reduction of approximately 50% after the initial doses. What is the standard maintenance dosing interval?

Answer: Every 6 months

After the initial dose and a second dose at 3 months, inclisiran is administered every 6 months, offering a major adherence advantage over monoclonal antibodies.

Which lipoprotein parameter is primarily reduced by bempedoic acid, and through what mechanism?

Answer: LDL-C, by inhibiting ATP citrate lyase upstream of HMG-CoA reductase in the liver

Bempedoic acid inhibits ATP citrate lyase (ACL), an enzyme upstream of HMG-CoA reductase in hepatic cholesterol synthesis, primarily lowering LDL-C.

A statin-intolerant patient with heterozygous FH is prescribed bempedoic acid. Which adverse effect unique to this drug class requires monitoring?

Answer: Hyperuricemia and gout flares

Bempedoic acid inhibits urate transporter activity, leading to elevated serum uric acid levels and increased risk of gout flares.

Evinacumab, an angiopoietin-like protein 3 (ANGPTL3) inhibitor, is approved for which patient population?

Answer: Homozygous familial hypercholesterolemia (HoFH) regardless of LDL receptor function

Evinacumab is FDA-approved for adults and pediatric patients ≥12 years with HoFH, notably effective even in those with non-functional LDL receptors.

Volanesorsen is an antisense oligonucleotide (ASO) approved for which specific lipid disorder?

Answer: Familial chylomicronemia syndrome (FCS) due to lipoprotein lipase deficiency

Volanesorsen targets APOC3 mRNA to reduce apolipoprotein C-III levels, thereby enhancing triglyceride clearance in patients with FCS.

Lomitapide's mechanism involves inhibiting microsomal triglyceride transfer protein (MTP). Which lipoprotein assembly step does this primarily disrupt?

Answer: Assembly and secretion of VLDL in the liver and chylomicrons in the intestine

MTP transfers triglycerides and phospholipids onto apolipoprotein B, which is essential for VLDL assembly in the liver and chylomicron assembly in the intestine; lomitapide blocks this step.