What are the effects of Ezetimibe (ezetimibe) on patients with high cholesterol?

Effects of Ezetimibe on Patients with High Cholesterol

Ezetimibe is 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

Mechanism of Action and Efficacy

• Ezetimibe works by inhibiting the Niemann-Pick C1-Like 1 (NPC1L1) protein in the small intestine, reducing cholesterol absorption by approximately 54% compared to placebo 2
• As monotherapy, ezetimibe reduces LDL-C by approximately 18%, making it a viable option for patients who cannot tolerate statins 1, 2
• When added to statin therapy, ezetimibe provides an incremental 25% reduction in LDL-C beyond what statins alone achieve 1, 2, 3
• The combination of ezetimibe with statins leads to greater reductions in total cholesterol, apolipoprotein B (ApoB), and non-HDL cholesterol compared to statin monotherapy 2, 4

Clinical Outcomes and Cardiovascular Benefits

• 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
• 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
• Ezetimibe helps more patients achieve LDL-C goals - one study showed 71.5% of patients receiving statin plus ezetimibe reached their goal compared to only 18.9% receiving statin plus placebo 3

Indications for Use

• FDA-approved 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, 2
• Recommended for patients who cannot achieve adequate LDL-C reduction with maximally tolerated statin therapy 1
• Particularly useful for patients with very high cardiovascular risk when LDL-C remains ≥70 mg/dL despite maximally tolerated statin therapy 1
• Indicated for patients with severe primary hypercholesterolemia whose LDL-C remains ≥100 mg/dL despite maximal tolerated statin therapy 1

Treatment Algorithm Based on Risk

1. For patients with very high cardiovascular risk:

   • Add ezetimibe when LDL-C remains ≥70 mg/dL despite maximally tolerated statin therapy 1
   • If LDL-C still remains ≥100 mg/dL after adding ezetimibe, consider adding a PCSK9 inhibitor 1

2. For patients with severe primary hypercholesterolemia:

   • Initial goal is to achieve ≥50% LDL-C reduction using high-intensity statin 1
   • Add ezetimibe when LDL-C remains ≥100 mg/dL despite maximally tolerated statin 1

3. For statin-intolerant patients:

   • Ezetimibe monotherapy can achieve approximately 18-20% reduction in LDL-C 1, 2, 5

Safety Profile and Adverse Effects

• Ezetimibe is generally well-tolerated with a safety profile similar to placebo when used as monotherapy 1, 2
• Common adverse effects with monotherapy include upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities 1, 2
• When combined with statins, common adverse effects include nasopharyngitis, myalgia, upper respiratory tract infection, arthralgia, and diarrhea 1, 2
• Cases of myopathy and rhabdomyolysis have been reported when ezetimibe is used alone or in combination with statin therapy, though these are rare 1
• Not recommended in patients with moderate to severe hepatic impairment 1, 2
• Monitor hepatic transaminases when used with statins, as persistent elevations may occur 1

Important Considerations and Contraindications

• 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, 2
• Ezetimibe does not adversely affect triglyceride levels and has minimal systemic absorption, resulting in few drug interactions 6
• No dosage adjustment necessary for patients with renal impairment 2

Dosing Information

• Standard dose is 10 mg orally once daily, with or without food 1, 2
• Can be taken at any time of day, independent of meals 2
• No dose adjustment required for elderly patients, despite slightly higher plasma concentrations 2