From the Guidelines
Zetia (ezetimibe) is effective in decreasing Low-Density Lipoprotein (LDL) cholesterol, but it has a minimal effect on increasing High-Density Lipoprotein (HDL) cholesterol. According to the most recent and highest quality study 1, ezetimibe works by inhibiting cholesterol absorption in the small intestine, which results in a significant reduction in LDL cholesterol levels. The study suggests that ezetimibe can reduce LDL-C levels by an average of 15-20% when used as monotherapy at the standard dose of 10 mg once daily. However, its effect on HDL cholesterol is quite modest, generally producing only a 1-3% increase at most.
Mechanism of Action
Ezetimibe specifically targets the Niemann-Pick C1-Like 1 protein, which is responsible for cholesterol uptake from the digestive tract. This mechanism of action is supported by a study published in the European Heart Journal 1, which highlights the benefits of combination therapy with ezetimibe and statins in reducing LDL-C and cardiovascular events.
Clinical Use
Zetia is often prescribed alongside statins for enhanced LDL-lowering effects, as the combination addresses both cholesterol production (statins) and absorption (ezetimibe). The medication is taken orally once daily with or without food, and patients should maintain a heart-healthy diet and exercise regimen while using it. Side effects are generally mild and may include diarrhea, joint pain, and rarely, liver enzyme elevations. Unlike statins, Zetia does not significantly affect triglyceride levels and is particularly useful for patients who cannot tolerate statins or need additional LDL reduction beyond what statins alone can provide.
Key Points
- Ezetimibe reduces LDL-C levels by 15-20% when used as monotherapy
- Ezetimibe has a minimal effect on increasing HDL cholesterol (1-3% increase)
- Combination therapy with ezetimibe and statins is recommended for patients who do not reach target LDL-C levels with statins alone
- Ezetimibe is particularly useful for patients who cannot tolerate statins or need additional LDL reduction beyond what statins alone can provide, as supported by a study published in the Annals of Internal Medicine 1 and the European Heart Journal 1.
From the FDA Drug Label
Ezetimibe Tablet reduces total cholesterol (total-C), LDL-C, apolipoprotein (Apo) B, and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with hyperlipidemia.
- Zetia (ezetimibe) decreases Low-Density Lipoprotein (LDL) cholesterol.
- However, the provided drug labels do not explicitly state that Zetia increases High-Density Lipoprotein (HDL) cholesterol 2, 2, 2.
From the Research
Zetia's Effect on LDL and HDL Cholesterol
- Zetia (ezetimibe) is a cholesterol absorption inhibitor that has been shown to decrease Low-Density Lipoprotein (LDL) cholesterol levels 3, 4, 5, 6, 7.
- Studies have demonstrated that ezetimibe can reduce LDL-cholesterol levels by 18% to 25% when used as monotherapy or in combination with statins 4, 5.
- However, the effect of Zetia on High-Density Lipoprotein (HDL) cholesterol is less clear, with some studies suggesting a potential increase in HDL-cholesterol levels 5, 6.
- One study found that ezetimibe add-on therapy significantly improved HDL-C levels, as well as other lipid parameters, in high-risk patients with hypercholesterolemia 5.
Mechanism of Action
- Ezetimibe works by inhibiting the intestinal absorption of cholesterol, which reduces the amount of cholesterol available for transport to the liver and subsequent release into the bloodstream 4, 6.
- This mechanism of action is distinct from that of statins, which inhibit cholesterol synthesis in the liver 3, 7.
- The combination of ezetimibe and statins has been shown to be more effective than statin monotherapy in lowering LDL-cholesterol levels and improving other lipid parameters 3, 4, 7.
Clinical Significance
- The clinical significance of Zetia's effects on LDL and HDL cholesterol is being evaluated in clinical outcome studies 6.
- Studies have demonstrated that ezetimibe can be a useful addition to statin therapy in patients who do not achieve their LDL-cholesterol goals with statins alone 3, 5, 7.
- The safety and efficacy of ezetimibe have been established in a range of patient populations, including those with primary hypercholesterolemia and homozygous familial hypercholesterolemia 4, 5.