Effects of Ezetimibe on Patients with High Cholesterol

Mechanism of Action and Efficacy

The American College of Cardiology recommends ezetimibe as an effective cholesterol-lowering medication that reduces LDL cholesterol by 18% as monotherapy and provides an additional 25% reduction when combined with statins, significantly improving cardiovascular outcomes in high-risk patients 1, 2, 3
As monotherapy, ezetimibe reduces LDL-C by approximately 18%, making it a viable option for patients who cannot tolerate statins 1
When added to statin therapy, ezetimibe provides an incremental 25% reduction in LDL-C beyond what statins alone achieve 1

The IMPROVE-IT trial demonstrated that adding ezetimibe to moderate-intensity statin therapy in patients with recent acute coronary syndrome reduced the primary composite endpoint of cardiovascular death, nonfatal MI, unstable angina requiring rehospitalization, coronary revascularization, and nonfatal stroke over a median follow-up of 6 years 1, 4
The SHARP trial showed that simvastatin plus ezetimibe reduced the primary endpoint of first major ASCVD events compared to placebo in patients with chronic kidney disease over a median follow-up of 4.9 years 1

The FDA approves ezetimibe as an adjunct to diet for reducing total cholesterol, LDL-C, ApoB, and non-HDL-C in patients with primary hyperlipidemia, either alone or in combination with statin therapy 1
The BMJ recommends ezetimibe for patients who cannot achieve adequate LDL-C reduction with maximally tolerated statin therapy 5, 6
Ezetimibe is particularly useful for patients with very high cardiovascular risk when LDL-C remains ≥70 mg/dL despite maximally tolerated statin therapy 5, 6
Ezetimibe is indicated for patients with severe primary hypercholesterolemia whose LDL-C remains ≥100 mg/dL despite maximal tolerated statin therapy 7, 8

For patients with very high cardiovascular risk, the BMJ recommends adding ezetimibe when LDL-C remains ≥70 mg/dL despite maximally tolerated statin therapy 5, 6
For patients with severe primary hypercholesterolemia, the initial goal is to achieve ≥50% LDL-C reduction using high-intensity statin, and then add ezetimibe when LDL-C remains ≥100 mg/dL despite maximally tolerated statin 7, 8

Ezetimibe is generally well-tolerated with a safety profile similar to placebo when used as monotherapy 1
Common adverse effects with monotherapy include upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities 1
Cases of myopathy and rhabdomyolysis have been reported when ezetimibe is used alone or in combination with statin therapy, though these are rare 1

Ezetimibe is contraindicated in patients with history of hypersensitivity to ezetimibe 1
No safety data in humans during pregnancy or lactation; avoid use in these populations 1
Drug interactions may occur with cyclosporine, fibrates, and bile acid sequestrants (take ezetimibe either ≥2 hours before or ≥4 hours after bile acid sequestrants) 1