CLS Non-Statin Lipid-Lowering Pharmacotherapy 1 — Questions and Answers
Question 1: What is the primary mechanism of action of ezetimibe?
- Inhibits HMG-CoA reductase in the liver
- Blocks cholesterol absorption at the Niemann-Pick C1-Like 1 (NPC1L1) transporter in the small intestine (Correct answer)
- Binds bile acids in the intestinal lumen to prevent reabsorption
- Activates peroxisome proliferator-activated receptor alpha (PPARα)
Correct answer: Blocks cholesterol absorption at the Niemann-Pick C1-Like 1 (NPC1L1) transporter in the small intestine
Ezetimibe selectively inhibits cholesterol absorption at the brush border of the small intestine by blocking the NPC1L1 transporter, reducing cholesterol delivery to the liver.
Question 2: Which bile acid sequestrant is FDA-approved for both hypercholesterolemia and as an adjunct treatment for type 2 diabetes?
- Cholestyramine
- Colestipol
- Colesevelam (Correct answer)
- Colestimide
Correct answer: Colesevelam
Colesevelam (Welchol) is the only bile acid sequestrant with dual FDA approval for LDL-C lowering and improving glycemic control in adults with type 2 diabetes mellitus.
Question 3: What is the expected LDL-C reduction with ezetimibe monotherapy?
- 5–10%
- 15–25% (Correct answer)
- 30–40%
- 45–55%
Correct answer: 15–25%
Ezetimibe monotherapy typically reduces LDL-C by approximately 15–25%, making it useful as adjunctive therapy rather than a standalone alternative to statins.
Question 4: Bile acid sequestrants are contraindicated in patients with triglyceride levels exceeding which threshold?
- 150 mg/dL
- 200 mg/dL
- 400 mg/dL (Correct answer)
- 1000 mg/dL
Correct answer: 400 mg/dL
Bile acid sequestrants can markedly increase triglyceride levels and are contraindicated when fasting triglycerides exceed 400 mg/dL due to the risk of acute pancreatitis.
Question 5: The IMPROVE-IT trial studied ezetimibe added to simvastatin in patients with recent acute coronary syndrome. What was the primary finding?
- No significant reduction in major adverse cardiovascular events
- A significant reduction in major adverse cardiovascular events (Correct answer)
- A reduction in all-cause mortality only
- An increase in hemorrhagic stroke risk
Correct answer: A significant reduction in major adverse cardiovascular events
IMPROVE-IT demonstrated that simvastatin plus ezetimibe significantly reduced the composite primary endpoint of major adverse cardiovascular events compared to simvastatin alone, validating the 'lower is better' hypothesis for LDL-C.
Question 6: What is the most clinically significant drug interaction concern with bile acid sequestrants?
- They increase systemic absorption of warfarin
- They bind and reduce intestinal absorption of many co-administered medications (Correct answer)
- They increase myopathy risk when combined with statins
- They increase bioavailability of thyroid hormones
Correct answer: They bind and reduce intestinal absorption of many co-administered medications
Bile acid sequestrants are positively charged resins that bind negatively charged molecules in the gut, reducing absorption of many drugs including warfarin, thyroid hormones, and fat-soluble vitamins; other medications should be taken 1 hour before or 4–6 hours after the sequestrant.
Question 7: Which of the following is NOT classified as a bile acid sequestrant?
- Cholestyramine
- Colestipol
- Colesevelam
- Ezetimibe (Correct answer)
Correct answer: Ezetimibe
Ezetimibe is a selective cholesterol absorption inhibitor acting at the NPC1L1 transporter, not a bile acid sequestrant; cholestyramine, colestipol, and colesevelam are all bile acid-binding resins.
CLS Non-Statin Lipid-Lowering Pharmacotherapy 1
What is the primary mechanism of action of ezetimibe?