Can statins and icosapent (icosapent ethyl) be initiated concurrently for hypertriglyceridemia?

From the Guidelines

Yes, statins and icosapent ethyl (Vascepa) can be initiated concurrently for hypertriglyceridemia, as this combination is often beneficial for patients with elevated triglyceride levels, particularly those with very high triglycerides (>500 mg/dL) or moderately elevated triglycerides (150-499 mg/dL) plus established cardiovascular disease or diabetes with additional risk factors. The typical dosing for icosapent ethyl is 2 grams twice daily with food, while statin dosing varies by specific medication (e.g., atorvastatin 10-80 mg daily, rosuvastatin 5-40 mg daily) 1. When starting both medications simultaneously, it's essential to monitor liver function tests and muscle symptoms, as statins can occasionally cause these side effects. This combination therapy works through complementary mechanisms - statins primarily lower LDL cholesterol and modestly reduce triglycerides (typically by 10-30%), while icosapent ethyl specifically targets triglycerides, reducing them by approximately 20-30% 1.

Some key points to consider when initiating this combination therapy include:

• Monitoring liver function tests and muscle symptoms due to potential statin side effects
• Starting with a moderate dose of statin and adjusting as needed to minimize side effects
• Ensuring patients understand the importance of adherence to both medications and lifestyle modifications
• Regularly assessing triglyceride levels and adjusting the treatment plan as necessary

The benefits of this combination therapy are supported by recent guidelines, including the 2021 ACC expert consensus decision pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia, which highlights the role of statin therapy in reducing triglycerides and ASCVD risk 1. Additionally, the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guidelines on the management of blood cholesterol in diabetes recommend considering the addition of icosapent ethyl to statin therapy in patients with diabetes and ASCVD or other cardiac risk factors, and with controlled LDL-C but elevated triglycerides (135-499 mg/dL) 1.

Overall, initiating statins and icosapent ethyl concurrently can be a valuable treatment strategy for patients with hypertriglyceridemia, particularly those at high risk for cardiovascular events, and should be considered in the context of individual patient needs and risk factors.

From the FDA Drug Label

In a drug-drug interaction study of 26 healthy adult subjects, icosapent ethyl 4 g/day at steady-state did not significantly change the steady-state AUCτ or Cmax of atorvastatin, 2-hydroxyatorvastatin, or 4-hydroxyatorvastatin when co-administered with atorvastatin 80 mg/day at steady-state.

• Concurrent initiation of statins and icosapent (icosapent ethyl) for hypertriglyceridemia is not directly addressed in the provided drug label.
• However, the label does mention a drug-drug interaction study with atorvastatin, which is a statin, and icosapent ethyl, showing no significant changes in atorvastatin pharmacokinetics when co-administered.
• No conclusion can be drawn regarding concurrent initiation, as the study only evaluated co-administration, not simultaneous initiation 2.

From the Research

Statins and Icosapent Ethyl for Hypertriglyceridemia

• The use of statins and icosapent ethyl (icosapent ethyl esters) for the management of hypertriglyceridemia has been studied in several clinical trials 3, 4, 5, 6, 7.
• Statins are generally considered the first-line treatment for hypertriglyceridemia, particularly in patients with elevated cardiovascular risk 3, 4, 5, 7.
• Icosapent ethyl may be considered for patients with residual hypertriglyceridemia despite statin therapy, particularly those with established cardiovascular disease or diabetes and elevated cardiovascular risk 4, 5, 6, 7.
• The REDUCE-IT trial demonstrated that icosapent ethyl significantly reduced cardiovascular events in patients with elevated triglyceride levels despite statin therapy 6.
• Current guidelines recommend the use of icosapent ethyl in patients with triglyceride levels between 135 and 499 mg/dL and established cardiovascular disease or diabetes with ≥2 cardiovascular risk factors, in addition to statin therapy 7.

Concurrent Initiation of Statins and Icosapent Ethyl

• There is no direct evidence to suggest that statins and icosapent ethyl cannot be initiated concurrently for the treatment of hypertriglyceridemia.
• However, the studies suggest that statins are typically initiated first, and icosapent ethyl is added to the treatment regimen if triglyceride levels remain elevated despite statin therapy 3, 4, 5, 6, 7.
• The decision to initiate statins and icosapent ethyl concurrently should be based on individual patient factors, including the severity of hypertriglyceridemia, cardiovascular risk, and other comorbidities.