Novel Lipid-Lowering Therapies Flashcards

A 45-year-old man with HoFH (no functional LDL receptors) is on maximum statin, ezetimibe, and PCSK9 inhibitor therapy but LDL-C remains 380 mg/dL. Which novel agent would most likely provide clinically meaningful LDL-C lowering in this scenario?

Answer: Evinacumab (ANGPTL3 inhibitor)

Evinacumab works independently of LDL receptor function by enhancing lipoprotein catabolism via LPL and EL disinhibition, making it effective in HoFH patients with non-functional receptors.

Which statement most accurately describes the cardiovascular outcomes data available for bempedoic acid?

Answer: CLEAR Outcomes trial showed 13% reduction in major adverse cardiovascular events vs. placebo in statin-intolerant patients

The CLEAR Outcomes trial demonstrated that bempedoic acid reduced MACE by approximately 13% versus placebo in statin-intolerant patients with or at high risk for ASCVD.

Zilebesiran is a novel GalNAc-conjugated siRNA targeting angiotensinogen. While primarily an antihypertensive, it is being studied in combination with what lipid-related rationale?

Answer: Reducing cardiometabolic risk through blood pressure control, potentially complementing lipid therapy in ASCVD prevention

Zilebesiran lowers blood pressure via RNAi-mediated angiotensinogen knockdown; its cardiometabolic risk reduction complements lipid-lowering strategies for comprehensive ASCVD prevention.

A patient develops severe injection-site reactions (ISRs) after starting inclisiran. According to the drug's labeling, how should ISRs be managed?

Answer: Rotate injection sites and apply ice; ISRs are generally mild, transient, and do not require discontinuation

ISRs with inclisiran are typically mild, self-limiting, and transient; rotating injection sites and symptomatic measures are recommended without needing to discontinue therapy.

Which of the following novel lipid-lowering agents is administered intravenously and approved specifically for HoFH?

Answer: Evinacumab (ANGPTL3 monoclonal antibody, intravenous)

Evinacumab is the only currently approved novel lipid-lowering agent administered intravenously (15 mg/kg IV every 4 weeks) and indicated for HoFH.

When counseling a patient about the lipid effects of icosapent ethyl (IPE) versus omega-3 acid ethyl esters (containing both EPA and DHA), which statement is most accurate?

Answer: IPE (EPA-only) demonstrated cardiovascular benefit in REDUCE-IT; DHA-containing formulations may raise LDL-C and lacked equivalent outcomes data

Pure EPA (IPE) demonstrated MACE reduction in REDUCE-IT, while DHA-containing omega-3 preparations may raise LDL-C and have not shown equivalent cardiovascular outcomes benefit.

A clinical lipid specialist is evaluating a patient with FCS (familial chylomicronemia syndrome) confirmed by genetic testing for LPL deficiency. After failure of dietary fat restriction and fibrates, which novel FDA-approved therapy should be considered?

Answer: Volanesorsen (APOC3 ASO)

Volanesorsen, an ASO targeting APOC3, is FDA-approved for adults with FCS, reducing TG levels significantly by enhancing LPL-mediated clearance of chylomicrons.