Can atorvastatin (Lipitor) 40mg and ezetimibe (Zetia) be used together?

From the Guidelines

Yes, atorvastatin 40mg and ezetimibe can be used together safely and effectively. This combination therapy is commonly prescribed for patients who need additional cholesterol-lowering effects beyond what statins alone can provide. Atorvastatin works by reducing cholesterol production in the liver, while ezetimibe works differently by decreasing cholesterol absorption in the intestines. Together, they provide complementary mechanisms that can lower LDL ("bad") cholesterol by 50-60% or more.

Key Points to Consider

• The standard dosing is typically atorvastatin 40mg once daily and ezetimibe 10mg once daily, both taken at the same time of day.
• Patients should be aware that this combination may slightly increase the risk of muscle-related side effects compared to either medication alone, so any unusual muscle pain, tenderness, or weakness should be reported to a healthcare provider.
• Regular blood tests to monitor liver function and lipid levels are recommended when taking this combination.
• This dual approach is particularly beneficial for patients with high cardiovascular risk who haven't reached their cholesterol goals with statin therapy alone, as supported by the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes 1.
• The IMPROVE IT trial demonstrated that the addition of ezetimibe to simvastatin reduced the relative risk of major adverse cardiovascular events (MACE) by 6.4% compared with placebo 1.
• The Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult 2021 also support the use of ezetimibe in addition to maximally tolerated statin therapy for patients with very high cardiovascular risk 1.

From the FDA Drug Label

Ezetimibe Tablet, added to on-going statin therapy, significantly lowered total-C, LDL-C, Apo B, and non-HDL-C compared with a statin administered alone LDL-C reductions induced by Ezetimibe Tablet were generally consistent across all statins When all patients receiving ezetimibe tablet with a statin were compared to all those receiving the corresponding statin alone, ezetimibe tablet significantly lowered total-C, LDL-C, Apo B, and non-HDL-C compared to the statin administered alone Atorvastatin 40 mg 66-32 -45 -37 -41 Ezetimibe Tablet + Atorvastatin 40 mg 65-42 -56 -45 -52

Yes, atorvastatin 40mg and ezetimibe can be used together.

• The combination of ezetimibe and atorvastatin has been shown to significantly lower total-C, LDL-C, Apo B, and non-HDL-C compared to atorvastatin alone 2.
• The LDL-C reductions induced by ezetimibe were consistent across all statins, including atorvastatin.
• The combination of ezetimibe and atorvastatin 40mg resulted in a mean percentage change from untreated baseline of -42% for total-C, -56% for LDL-C, -45% for Apo B, and -52% for non-HDL-C.

From the Research

Combination Therapy of Atorvastatin and Ezetimibe

• Atorvastatin 40mg and ezetimibe can be used together to effectively lower LDL cholesterol levels in patients with hypercholesterolemia 3, 4, 5.
• Studies have shown that the combination of atorvastatin and ezetimibe is more effective than uptitrating atorvastatin alone in reducing LDL cholesterol levels 3, 4.
• The addition of ezetimibe to atorvastatin has been shown to significantly reduce LDL cholesterol levels, as well as other lipid parameters such as total cholesterol, triglycerides, and apolipoprotein B 3, 4, 5.

Efficacy and Safety

• The combination of atorvastatin and ezetimibe has been shown to be generally well tolerated, with similar safety and tolerability profiles to atorvastatin alone 3, 4.
• The incidence of liver and muscle adverse experiences was similar between the combination therapy and atorvastatin alone 3.
• The combination of atorvastatin and ezetimibe has been shown to be effective in reducing LDL cholesterol levels in various patient populations, including those at high risk for coronary heart disease and those with atherosclerotic cardiovascular disease 6, 7.

Patient Subgroups

• The efficacy of the combination of atorvastatin and ezetimibe has been shown to be consistent across different age, gender, and race subgroups 7.
• The combination therapy has been shown to be effective in reducing LDL cholesterol levels in patients with moderately high or high risk for coronary heart disease, regardless of age, gender, or race 7.