Non-Statin Lipid-Lowering Pharmacotherapy Flashcards

What is the primary mechanism of action of fibrates?

Answer: Activate peroxisome proliferator-activated receptor alpha (PPARα)

Fibrates activate PPARα, a nuclear receptor that increases lipoprotein lipase expression, reduces apoC-III production, and increases apoA-I synthesis, resulting in reduced triglycerides and increased HDL-C.

Which fibrate–statin combination carries the greatest risk of severe myopathy and rhabdomyolysis?

Answer: Gemfibrozil + any statin

Gemfibrozil inhibits the glucuronidation pathway responsible for statin metabolism, raising statin plasma concentrations significantly and increasing the risk of myopathy and rhabdomyolysis; fenofibrate does not share this interaction.

For which lipid abnormality are fibrates considered first-line pharmacotherapy?

Answer: Severe hypertriglyceridemia (≥500 mg/dL)

Fibrates reduce triglycerides by 20–50% and are indicated as first-line pharmacotherapy for severe hypertriglyceridemia (≥500 mg/dL) to reduce pancreatitis risk.

What is the most notable lipid effect of niacin (nicotinic acid) compared to other lipid-lowering agents?

Answer: Greatest HDL-C increase

Niacin raises HDL-C by 15–35%, which is the largest HDL-C increase achievable with any single pharmacologic agent currently available.

What did the AIM-HIGH and HPS2-THRIVE trials of extended-release niacin in statin-treated patients demonstrate?

Answer: No additional cardiovascular benefit and increased adverse events

Both AIM-HIGH and HPS2-THRIVE found no cardiovascular benefit from adding niacin to statin therapy and documented increased adverse events including hepatotoxicity and serious infections, substantially reducing niacin's clinical use.

What is the most common adverse effect of niacin, and what can reduce its severity?

Answer: Cutaneous flushing; reduced by taking aspirin 30 minutes before the dose

Cutaneous flushing (prostaglandin D2-mediated vasodilation) occurs in up to 75% of patients taking niacin and can be significantly attenuated by taking 325 mg aspirin 30 minutes before the niacin dose.

Fenofibrate requires dose adjustment or avoidance in patients with which condition?

Answer: Chronic kidney disease or renal impairment

Fenofibrate is primarily renally eliminated and can worsen renal function; dose reduction is required for eGFR <60 mL/min/1.73m², and it should be avoided in severe renal impairment (eGFR <30 mL/min/1.73m²).