Intervention

Ezetimibe

Last updated Sat May 30 2026 00:00:00 GMT+0000 (Coordinated Universal Time)

RCT evidence— IMPROVE-IT outcomes trial

What it is

Ezetimibe selectively inhibits the Niemann-Pick C1-Like 1 (NPC1L1) transporter at the brush border of the small intestine, reducing absorption of dietary and biliary cholesterol. The compensatory increase in LDL receptor expression on hepatocytes lowers plasma LDL by 15–25%.

What the evidence shows

IMPROVE-IT (2015): added to simvastatin after acute coronary syndrome, reduced major adverse cardiovascular events 6.4% relative vs placebo — the trial that established additional LDL lowering beyond statin alone provides additional benefit.
Loop closed with the "lower LDL is better" principle from statin and PCSK9 trials.
Excellent safety profile.

When it’s used

LDL still above target on maximum-tolerated statin.
Statin intolerance (works as monotherapy with reduced effect).
Combined with bempedoic acid for statin-intolerant adults.

References

Cannon, C. P. et al. Ezetimibe added to statin therapy after acute coronary syndromes (IMPROVE-IT). N. Engl. J. Med. 372, 2387–2397 (2015).