What is the use of Ezetimibe (EZETIMIBE)?

From the Guidelines

Ezetimibe should be considered as an adjunct to diet and statin therapy to lower LDL-C levels in patients with atherosclerotic cardiovascular disease (ASCVD) risk, with a recommended dose of 10 mg orally daily, as it has been shown to reduce LDL-C levels by 18% as monotherapy and by an additional 25% when used in combination with statin therapy 1. The medication works by inhibiting the NPC1L1 protein, reducing cholesterol absorption in the small intestine. According to the 2022 ACC expert consensus decision pathway, ezetimibe is a nonstatin agent that may be used to manage LDL-related ASCVD risk, with a mean percentage reduction in LDL-C of 18% as monotherapy and 25% in combination with statin therapy 1. Key considerations for prescribing ezetimibe include:

• Contraindications: history of hypersensitivity to the medication
• Warnings and precautions: not recommended in patients with moderate to severe hepatic impairment, and monitoring of hepatic transaminases is recommended when used in combination with statin therapy
• Adverse effects: upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities as monotherapy, and nasopharyngitis, myalgia, upper respiratory tract infection, arthralgia, and diarrhea in combination with statin therapy
• Drug-drug interactions: cyclosporine, fibrates, and bile acid sequestrants Ezetimibe has been studied in several cardiovascular outcomes trials, including the IMPROVE-IT trial, which demonstrated that the addition of ezetimibe to moderate-intensity statin therapy reduced the primary composite endpoint of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization, or nonfatal stroke 1. Overall, ezetimibe is a valuable option for patients with ASCVD risk who require additional LDL-C lowering beyond statin therapy, and its use should be considered in accordance with the latest clinical guidelines and patient-specific factors 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. Ezetimibe tablets is a medicine used with a cholesterol lowering diet: and with other cholesterol medicines called a statin, or alone (when additional cholesterol lowering treatments are not possible), to lower elevated low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in adults with primary hyperlipidemia (too many fats in your blood), including heterozygous familial hypercholesterolemia (HeFH). 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) 2.

• Ezetimibe is used with a cholesterol lowering diet and with other cholesterol medicines called a statin, or alone.
• It 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.

From the Research

Ezetimide Overview

• Ezetimide is a cholesterol-lowering drug that can be used in combination with statins to achieve additional low-density lipoprotein cholesterol (LDL-C) lowering 3, 4.
• The combination of ezetimide and statins has been shown to be effective in reducing the risk of major cardiovascular events, with an additional LDL-C lowering of 25% or total LDL-C lowering of 34-61% 3.
• Ezetimide is one of the few hypolipemic medications that leads to additional atherosclerotic cardiovascular disease (ASCVD) risk reduction when added to statin therapy 3.

Mechanism of Action

• Ezetimide inhibits cholesterol absorption, which can lead to a decrease in LDL-C by about 10-18% and Apo B by 11-16% 3.
• The addition of ezetimide to statin therapy can also lead to pleotropic anti-inflammatory and antioxidative effects, which can contribute to the added ASCVD risk reduction 3.

Clinical Use

• Ezetimide can be used in patients who fail to achieve target LDL-C levels with statin monotherapy, or in patients who experience statin-associated muscle symptoms 3, 4.
• The combination of ezetimide and statins is relatively safe, with no significant increase in adverse effects 3.
• Ezetimide remains a very important combination partner for statins, with continuously increasing treatment numbers 5.

Comparison with Other Treatments

• The effectiveness of combination therapy with statin and ezetimide compared with intensified statin monotherapy has been evaluated in several studies, with results suggesting that the combination therapy can be an effective alternative for patients who do not tolerate or respond to high-intensity statin monotherapy 6, 7.
• Ezetimide has been shown to be more effective than other lipid-modifying agents, such as bile acid sequestrants and fibrates, in achieving additional LDL-C lowering when added to statin therapy 6, 7.