Can ezetimibe be given with atorvastatin (Lipitor)?

From the Guidelines

Yes, ezetimibe can be given with atorvastatin, as this combination is commonly prescribed to help lower cholesterol levels more effectively than either medication alone, with a mean percentage reduction in LDL-C of 25% when used together 1.

Mechanism of Action and Dosage

Ezetimibe works in the intestine to reduce cholesterol absorption, while atorvastatin is a statin that works in the liver to reduce cholesterol production. Ezetimibe is typically dosed at 10 mg once daily, and atorvastatin is available in doses ranging from 10-80 mg once daily.

Clinical Evidence and Guidelines

The use of ezetimibe in combination with statin therapy, such as atorvastatin, is supported by clinical evidence, including the IMPROVE-IT trial, which demonstrated a reduction in cardiovascular events with the addition of ezetimibe to simvastatin in patients with recent acute coronary syndrome 2.

Safety and Monitoring

The combination of ezetimibe and atorvastatin is generally well-tolerated, though patients should be monitored for potential side effects, including muscle pain or liver function abnormalities.

Key Considerations

• The combination is particularly useful for patients who haven't reached their cholesterol goals on maximum tolerated statin therapy alone or who experience side effects at higher statin doses.
• Both medications are typically taken once daily, and they can be taken at the same time regardless of meals, though atorvastatin is often taken in the evening.
• The 2022 ACC expert consensus decision pathway recommends the use of ezetimibe as an adjunct to diet to reduce LDL-C levels in patients with primary hyperlipidemia, either alone or in combination with statin therapy 1.
• The guidelines also recommend considering the addition of ezetimibe to statin therapy in patients with severe primary hypercholesterolemia or those who have not achieved desired LDL-C lowering with maximally tolerated statin therapy alone 3.

From the FDA Drug Label

In combination with a statin, or alone when additional low density lipoprotein cholesterol (LDL-C) lowering therapy is not possible, as an adjunct to diet to reduce elevated LDL-C in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) In combination with a statin as an adjunct to diet to reduce elevated LDL-C in pediatric patients 10 years of age and older with HeFH. In combination with a statin, and other LDL-C lowering therapies, to reduce elevated LDL-C levels in adults and in pediatric patients 10 years of age and older with homozygous familial hypercholesterolemia (HoFH) A trial was conducted to assess the efficacy of ezetimibe tablet in the treatment of HoFH This double-blind, randomized, 12-week trial enrolled 50 patients (age range 11 to 74 years, 58% female; 90% White, 2% Black or African American, 8% other races identified as Hispanic or Latino) with a clinical and/or genotypic diagnosis of HoFH, with or without concomitant LDL apheresis, already receiving atorvastatin or simvastatin (40 mg) Patients were randomized to one of three treatment groups, atorvastatin or simvastatin (80 mg), ezetimibe tablet administered with atorvastatin or simvastatin (40 mg), or ezetimibe tablet administered with atorvastatin or simvastatin (80 mg)

Ezetimibe can be given with atorvastatin. The FDA drug label for ezetimibe indicates that it can be used in combination with a statin, such as atorvastatin, to reduce elevated LDL-C levels in adults and pediatric patients with primary hyperlipidemia, HeFH, and HoFH 4. In a clinical trial, ezetimibe was administered with atorvastatin to patients with HoFH, and the combination significantly reduced LDL-C levels compared to atorvastatin monotherapy 5.

From the Research

Combination of Ezetimibe and Atorvastatin

• The combination of ezetimibe and atorvastatin has been evaluated for the treatment of hypercholesterolemia, with studies showing that ezetimibe can be combined with any dose of atorvastatin for incremental lipid-lowering effects 6.
• Clinical benefits have been seen with ezetimibe combined with simvastatin, and studies of its combination with atorvastatin have generally shown that the addition of ezetimibe to atorvastatin is more effective than titrating the atorvastatin dose 6.
• The ezetimibe-atorvastatin combination has been shown to be effective in reducing atherogenic lipids and is well tolerated, with fixed-dose combinations improving medication adherence 6.

Efficacy and Safety

• Studies have compared the efficacy and safety of ezetimibe/simvastatin combination versus atorvastatin alone in adults ≥65 years of age with hypercholesterolemia, showing that ezetimibe/simvastatin provided significantly greater improvements in key lipid parameters and higher attainment of LDL cholesterol targets than atorvastatin, with comparable tolerability 7.
• The addition of ezetimibe to simvastatin, atorvastatin, or rosuvastatin therapy has been shown to result in greater LDL-C reductions and goal attainment than titrating these statins 8.
• Switching to ezetimibe/simvastatin 10/20 mg has been shown to be more effective at reducing LDL-C, total cholesterol, and Apo B versus doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg, regardless of metabolic syndrome status 9.

Clinical Implications

• The combination of ezetimibe and atorvastatin may be a useful treatment option for patients who cannot reach their lipid targets with maximally tolerated statin doses 6.
• The efficacy and safety of ezetimibe/atorvastatin combination make it a potential treatment strategy for patients with hypercholesterolemia, particularly those at high risk for cardiovascular events 6, 7, 8, 9.