What is the use of Ezetimibe (Zetia)?

From the Guidelines

Ezetimibe should be prescribed at a dose of 10 mg once daily, with or without food, for patients with atherosclerotic cardiovascular disease (ASCVD) who require additional LDL-C lowering beyond statin therapy, as it provides an additional 15-20% reduction in LDL cholesterol and has been shown to reduce cardiovascular events in clinical trials, such as IMPROVE-IT 1.

Key Points

• Ezetimibe works by inhibiting the NPC1L1 protein, reducing cholesterol absorption in the small intestine.
• It is often used in combination with statins for enhanced cholesterol reduction, and can be used as monotherapy in patients who cannot tolerate statins.
• The medication is generally well-tolerated, with common side effects including diarrhea, joint pain, and rarely, liver enzyme elevations.
• Regular lipid panel monitoring is recommended to assess effectiveness, typically 4-12 weeks after starting therapy.

Clinical Considerations

• Ezetimibe is FDA-approved for use as an adjunct to diet to reduce LDL-C, total cholesterol, ApoB, and non-HDL-C in patients with primary hyperlipidemia, either alone or in combination with statin therapy 1.
• The 2022 ACC expert consensus decision pathway recommends considering the addition of ezetimibe to maximally tolerated statin therapy in patients with ASCVD and baseline LDL-C ≥ 190 mg/dL who did not achieve ≥ 50% LDL-C reduction and LDL-C < 70 mg/dL on maximally tolerated statin therapy in combination with nonstatin therapy 1.
• The Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult 2021 recommend adding ezetimibe to maximally tolerated statin therapy when LDL cholesterol level remains ≥ 70 mg/dL in patients with very high cardiovascular risk, and considering the addition of a PCSK9 inhibitor if the LDL cholesterol level on maximally tolerated statin and ezetimibe therapy remains ≥ 100 mg/dL 1.

From the FDA Drug Label

For patients treated with ezetimibe tablet, mean plasma levels of plant sterols were reduced progressively over the course of the trial. Reductions in sitosterol and campesterol were consistent between patients taking ezetimibe tablet concomitantly with bile acid sequestrants (n=8) and patients not on concomitant bile acid sequestrant therapy (n=21) The main use of ezetimibe is to lower elevated low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH). Ezetimibe is also used to lower elevated sitosterol and campesterol levels in adults and in children 9 years of age and older with homozygous familial sitosterolemia.

• Key benefits of ezetimibe include:
  • Lowering LDL-C levels
  • Reducing plasma levels of plant sterols, including sitosterol and campesterol
  • Used in combination with other cholesterol-lowering medicines, such as statins and fenofibrate, to achieve optimal cholesterol levels 2

From the Research

Ezetimibe Overview

• Ezetimibe is a cholesterol-lowering drug that can be used in combination with statins to reduce low-density lipoprotein (LDL) cholesterol levels 3, 4.
• The combination of ezetimibe and statin therapy has been shown to be effective in reducing LDL cholesterol levels and achieving target lipid values in patients with high cardiovascular risk 3, 5.
• Ezetimibe can also be used in patients who are intolerant to statins, and can be combined with other non-statin therapies such as bempedoic acid to reduce LDL cholesterol levels 6, 7.

Efficacy of Ezetimibe

• Studies have shown that ezetimibe can lower LDL cholesterol levels by 10-18% when used as monotherapy, and by 25% or more when used in combination with statins 4, 5.
• Ezetimibe has also been shown to reduce the risk of major adverse cardiovascular events (MACE) in patients with high cardiovascular risk 4, 7.
• The combination of ezetimibe and statin therapy has been shown to be more effective than double-dose statin monotherapy in reducing LDL cholesterol levels and achieving target lipid values 5.

Safety of Ezetimibe

• Ezetimibe has been shown to be generally well-tolerated, with a favorable side effect profile compared to statins 4, 6.
• The combination of ezetimibe and statin therapy has been shown to be safe and effective, with no significant increase in laboratory-related adverse events compared to statin monotherapy 5.
• Ezetimibe can be used in combination with other non-statin therapies, such as bempedoic acid, to reduce LDL cholesterol levels and achieve target lipid values in patients who are intolerant to statins 6, 7.