From the Guidelines
Ezetimibe is not the preferred treatment for hypertriglyceridemia due to its limited effectiveness, with only a 5-10% reduction in triglyceride levels, as shown in a study published in Circulation 1.
Treatment Options for Hypertriglyceridemia
Other medications are generally more effective first-line choices for hypertriglyceridemia, including:
- Fibrates (like fenofibrate 145mg daily), which can reduce triglycerides by 30-50% 1
- Omega-3 fatty acids (2-4g daily), which can reduce triglycerides by 20-50% 1
- Niacin, which can reduce triglycerides by 20-50% 1
- Statins, which may also be considered, especially if LDL cholesterol is also elevated, and can reduce triglycerides by 10-30% 1
Role of Ezetimibe in Hypertriglyceridemia Management
Ezetimibe (10mg daily) might be added to these therapies in patients who also have elevated LDL cholesterol, but it shouldn't be used alone for triglyceride management, as recommended in the 2021 ACC expert consensus decision pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia 1. The limited effect of ezetimibe on triglycerides occurs because it targets intestinal cholesterol absorption rather than directly affecting triglyceride metabolism in the liver, which is the primary site for triglyceride production and clearance.
Clinical Guidelines and Recommendations
The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol also supports the use of ezetimibe as an adjunct to statin therapy in patients with elevated LDL cholesterol, but not as a primary treatment for hypertriglyceridemia 1.
From the Research
Ezetimibe and Hypertriglyceridemia
- Ezetimibe is a selective cholesterol-absorption inhibitor that reduces low-density lipoprotein cholesterol (LDL-C) by approximately 15 to 20% when used as monotherapy or in combination with other lipid-lowering medications 2.
- Unlike other lipid-lowering medications, ezetimibe does not appear to worsen hypertriglyceridemia 2.
- The effect of ezetimibe on hypertriglyceridemia is not fully understood, and further studies are needed to determine its efficacy in reducing triglyceride levels 3.
Combination Therapy with Ezetimibe
- The combination of ezetimibe and fenofibrate has been shown to be effective in reducing LDL-C and triglyceride levels in patients with mixed hyperlipidemia 4, 5.
- The EFECTL study demonstrated that long-term coadministration of fenofibrate and ezetimibe resulted in significant reductions in LDL cholesterol and triglycerides, with a good safety profile 5.
- The combination therapy may be beneficial for patients with hypertriglyceridemia who require additional reduction in triglyceride-rich lipoproteins and remnant particles 6.
Efficacy and Safety of Ezetimibe
- Ezetimibe has been shown to be safe and effective in reducing LDL-C levels, with an adverse-event profile similar to placebo when used as monotherapy or in combination with statins and fenofibrate 2.
- Further studies are needed to determine the long-term safety and efficacy of ezetimibe, particularly in combination with other lipid-lowering medications 2, 3, 4.