Ezetimibe is a cholesterol absorption inhibitor used to lower LDL cholesterol.

It is most commonly used:

• As add-on therapy to statins • In statin intolerance • When additional LDL reduction is required

Ezetimibe is not first-line monotherapy for most patients. It is an adjunct drug.

Ezetimibe inhibits the NPC1L1 transporter in the small intestine.

Result:

• ↓ Absorption of dietary cholesterol • ↓ Absorption of biliary cholesterol • ↓ Delivery of cholesterol to the liver • ↑ LDL receptor expression • ↓ Circulating LDL levels

Primary effect: LDL reduction (~15–20%)

Unlike statins, ezetimibe does not inhibit cholesterol synthesis.

If LDL remains above target despite maximally tolerated statin:

→ Add ezetimibe before escalating to PCSK9 inhibitors in most patients.

This strategy is supported by outcome data.

For patients unable to tolerate adequate statin dosing:

• Ezetimibe provides modest LDL reduction • Can be combined with low-dose statin

IMPROVE-IT trial:

• Ezetimibe + simvastatin • Reduced cardiovascular events compared to statin alone • Modest but statistically significant benefit

Ezetimibe is not as potent as statins, but it provides incremental risk reduction.

• Oral administration • Once daily dosing • Minimal CYP450 interaction • Well tolerated

Metabolized via glucuronidation.

Generally well tolerated.

Possible:

• Mild GI upset • Rare transaminase elevation (especially with statin combination) • Rare myalgias

Lower myopathy risk than statins.

• Bile acid sequestrants may reduce absorption • Separate dosing if used together

Minimal CYP interaction.

✔ Adds ~15–20% LDL reduction ✔ Best used with statins ✔ Safe and well tolerated ✔ Modest but real outcome benefit ✔ Step before PCSK9 in most treatment algorithms

Next: More aggressive LDL lowering options

→ PCSK9 Inhibitors

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