Novel Lipid-Lowering Therapies Flashcards

In the ORION-10 trial of inclisiran, what was the approximate mean LDL-C percent reduction from baseline at day 510?

Answer: 50–55%

ORION-10 demonstrated a sustained time-averaged LDL-C reduction of approximately 52% from baseline with inclisiran in patients with ASCVD.

A 58-year-old woman with ASCVD and statin myalgia is started on bempedoic acid/ezetimibe combination tablet. Which statement best describes the additive mechanism?

Answer: Bempedoic acid reduces hepatic synthesis while ezetimibe blocks intestinal cholesterol absorption via NPC1L1

The complementary mechanisms—hepatic synthesis inhibition by bempedoic acid and intestinal absorption inhibition by ezetimibe via NPC1L1—produce additive LDL-C lowering.

ANGPTL3 inhibition by evinacumab lowers LDL-C through which primary pathway?

Answer: Enhancing lipoprotein lipase (LPL) and endothelial lipase (EL) activity to accelerate lipoprotein catabolism

ANGPTL3 normally inhibits both LPL and endothelial lipase; evinacumab removes this inhibition, accelerating catabolism of triglyceride-rich and LDL particles.

Which of the following novel therapies specifically targets Lp(a) and is currently in advanced clinical development for cardiovascular risk reduction?

Answer: Pelacarsen / olpasiran (anti-Lp(a) ASO or siRNA)

Pelacarsen (an ASO) and olpasiran (a siRNA) both specifically target Lp(a) synthesis and are in Phase 3 cardiovascular outcomes trials.

A patient with HoFH on lomitapide develops elevated transaminases (ALT 4× ULN) after 4 months. What is the recommended management?

Answer: Suspend lomitapide, recheck LFTs within 1 week, and resume at a lower dose if enzymes normalize

Per lomitapide prescribing information and REMS program guidance, dose modification and monitoring is indicated for ALT/AST ≥3× ULN; suspension with reassessment guides safe resumption.

Obicetrapib inhibits CETP (cholesteryl ester transfer protein). What is the expected lipid panel effect?

Answer: Increased HDL-C and decreased LDL-C

CETP inhibition reduces the transfer of cholesterol esters from HDL to LDL/VLDL, resulting in increased HDL-C and decreased LDL-C.

Mipomersen is an ASO targeting APOB mRNA. For which patient population was it FDA-approved, and what limits its wider use?

Answer: HoFH adults; limited by hepatotoxicity risk and REMS program requirements

Mipomersen is FDA-approved for HoFH in adults but requires a REMS program due to hepatotoxicity risk, restricting its clinical use.