====== Ezetimibe ======

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.

----

===== Mechanism of Action =====

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.

----

===== Clinical Role =====

==== 1. Add-On to Statins ====

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.

----

==== 2. Statin Intolerance ====

For patients unable to tolerate adequate statin dosing:

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

----

===== Outcome Evidence =====

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.

----

===== Pharmacokinetics =====

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

Metabolized via glucuronidation.

----

===== Adverse Effects =====

Generally well tolerated.

Possible:

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

Lower myopathy risk than statins.

----

===== Drug Interactions =====

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

Minimal CYP interaction.

----

===== Clinical Pearls =====

✔ 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

→ [[cardio:lipids:pcsk9|PCSK9 Inhibitors]]

Return to lipid module:

→ [[cardio:lipids:start|Back to Antilipemics]]