Ezetimibe — The Cholesterol Absorption Inhibitor
Ezetimibe is a lipid-lowering medication that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. By lowering circulating low-density lipoprotein (LDL) cholesterol and apolipoprotein B, it reduces the risk of atherosclerotic cardiovascular disease, a primary driver of age-related mortality.
Mechanism of Action
Ezetimibe localises at the brush border of the small intestine and inhibits the Niemann-Pick C1-Like 1 (NPC1L1) sterol transporter. This blocks the vesicular endocytosis of cholesterol into enterocytes, decreasing the delivery of intestinal cholesterol to the liver. The reduced hepatic cholesterol pool triggers an upregulation of LDL receptors, enhancing the clearance of LDL cholesterol from the blood. Unlike statins, ezetimibe does not inhibit cholesterol synthesis in the liver.
Human Trial Evidence
Ezetimibe has been extensively studied in large-scale human cardiovascular outcome trials. The landmark IMPROVE-IT trial (2015) demonstrated that adding ezetimibe to statin therapy significantly lowered LDL cholesterol and reduced the incidence of cardiovascular events in patients after acute coronary syndromes. The EWTOPIA 75 trial also showed primary prevention benefits in elderly patients over 75 years old.
Dosing Protocol
The standard dose is 10 mg taken orally once daily, with or without food. It is available by prescription only. No dosage adjustment is required for mild hepatic impairment or renal insufficiency.
Safety & Contraindications
Ezetimibe is generally well tolerated, with a safety profile similar to placebo in monotherapy. When co-administered with a statin, it is contraindicated in patients with active liver disease or unexplained persistent elevations in hepatic transaminases. Rare adverse effects include myopathy, elevated liver enzymes, and gastrointestinal upset. It should not be used with cyclosporine without close monitoring.