What is the role of Omega-3 (fatty acids) prescription in lowering hypercholesterolemia (high cholesterol)?

From the Guidelines

Prescription-strength omega-3s, such as Vascepa (icosapent ethyl) and Lovaza (omega-3-acid ethyl esters), can help reduce triglycerides at doses of 2-4 grams daily, but they have limited effects on LDL (bad) cholesterol, and their use should be considered on a case-by-case basis, taking into account the potential benefits and risks, as noted in the 2021 ACC expert consensus decision pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia 1.

Key Points to Consider

• The primary medication choice for cholesterol management remains statins, with options like atorvastatin (10-80mg daily) or rosuvastatin (5-40mg daily) 1.
• Omega-3 fatty acid supplements are not typically recommended as a first-line treatment for lowering cholesterol, and nonprescription fish oil products are not interchangeable with prescription omega-3 products 1.
• The mechanism behind omega-3 benefits involves reducing liver production of triglycerides and VLDL cholesterol while providing anti-inflammatory effects 1.
• For optimal heart health, combine any medication with lifestyle changes including a Mediterranean diet, regular exercise, weight management, and smoking cessation 1.

Important Considerations

• Prescription omega-3 fatty acid preparations have been shown to increase the risk of atrial fibrillation (AF) at higher doses (1.8 to 4 g daily) 1.
• The use of omega-3 fatty acids should be individualized, taking into account the patient's specific risk factors and medical history 1.
• The 2018 AHA/ACC/multisociety cholesterol guideline recommends that if triglycerides are persistently elevated or increasing, it is reasonable to further reduce triglycerides by the addition of prescription omega-3 fatty acids (IPE or omega-3 acid ethyl esters) 1.

From the FDA Drug Label

Omega-3-acid ethyl esters capsules, USP are indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (greater than or equal to 500 mg per dL) hypertriglyceridemia (HTG) The effects of omega-3-acid ethyl esters 4 grams per day were assessed in 2 randomized, placebo-controlled, double-blind, parallel-group trials of 84 adult subjects (42 on omega-3-acid ethyl esters, 42 on placebo) with very high triglyceride levels Omega-3-acid ethyl esters 4 grams per day reduced median TG, VLDL-C, and non-HDL-C levels and increased median HDL-C from baseline relative to placebo Treatment with omega-3-acid ethyl esters to reduce very high TG levels may result in elevations in LDL-C and non-HDL-C in some individuals.

The role of Omega-3 (fatty acids) prescription in lowering hypercholesterolemia (high cholesterol) is to reduce triglyceride levels in adult patients with severe hypertriglyceridemia.

• Key benefits:
  • Reduces median TG, VLDL-C, and non-HDL-C levels
  • Increases median HDL-C from baseline relative to placebo
• Important consideration: Treatment with omega-3-acid ethyl esters may result in elevations in LDL-C and non-HDL-C in some individuals, and patients should be monitored to ensure that the LDL-C level does not increase excessively 2.

From the Research

Role of Omega-3 Fatty Acids in Lowering Hypercholesterolemia

• Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to effectively reduce triglyceride levels and may impact cardiovascular outcomes 3, 4, 5, 6, 7
• Prescription omega-3 fatty acids have been approved by the United States Food and Drug Administration as an adjunct to diet for the treatment of very high triglyceride levels 3, 6
• The active ingredients of omega-3 fatty acids, EPA and DHA, are responsible for the triglyceride-lowering effect, with a recommended daily dose of 2-4 g/day 3, 6

Efficacy of Omega-3 Fatty Acids in Hypertriglyceridemia

• Studies have demonstrated that omega-3 fatty acids can reduce triglyceride levels by 25-45% and very-low-density-lipoprotein cholesterol levels by more than 50% in patients with very high triglyceride levels 3, 6, 7
• Omega-3 fatty acids have also been shown to reduce non-high-density lipoprotein cholesterol levels, which is a better predictor of atherogenic risk compared to low-density lipoprotein cholesterol alone 5
• However, omega-3 fatty acids may increase low-density lipoprotein cholesterol levels in some patients, particularly those with high baseline triglyceride levels 3, 4, 5

Safety and Tolerability of Omega-3 Fatty Acids

• Prescription omega-3 fatty acids have been well tolerated in clinical trials, with a low rate of adverse events and treatment-associated discontinuations 3, 4, 6, 7
• Common gastrointestinal side effects, such as abdominal pain, nausea, and diarrhea, have been reported with omega-3-carboxylic acid (Epanova) 7
• The safety and efficacy of omega-3 fatty acids in patients with hypertriglyceridemia have been established, but long-term outcomes trials are needed to clarify the potential cardiovascular benefits 4, 7