Ezetimibe
Cholesterol absorption inhibitor · “The gut gatekeeper”
The Clinical Case
Female, 66 yo. Known CAD on rosuvastatin 40 mg. LDL still 2.1 mmol/L despite maximal statin dose (target <1.4). No statin side effects. Cardiologist adds a once-daily oral agent that blocks cholesterol absorption in the small intestine, has no CYP450 interactions, and whose combination with a statin was tested in the IMPROVE-IT trial.
The Answer
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Clinical Pearl
Mechanism: Inhibits NPC1L1 transporter on enterocytes — blocks dietary and biliary cholesterol absorption; LDL↓ ~18–20%
All Hints
Mechanism: Inhibits NPC1L1 transporter on enterocytes — blocks dietary and biliary cholesterol absorption; LDL↓ ~18–20%
Synergy: Compensatory hepatic LDL receptor upregulation on statin → additive LDL lowering; IMPROVE-"IT": +6% RRR in post-ACS
Pharmacokinetics: Enterohepatic recycling of glucuronide metabolite; half-life 22 h; once daily; no CYP interactions
Monotherapy: First-line add-on in familial hypercholesterolaemia; useful when statins are not tolerated
Safety: Excellent safety profile; safe in renal failure; avoid in moderate-severe hepatic impairment
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