Can fenofibrate be added to HMG-CoA reductase inhibitors (statins) to control severely elevated triglycerides, specifically hypertriglyceridemia?

From the Guidelines

Fenofibrate can be considered for addition to statin therapy to control severely elevated triglycerides, specifically hypertriglyceridemia, when the benefits of ASCVD risk reduction or triglyceride lowering outweigh the potential risk for adverse effects, as stated in the 2013 ACC/AHA guideline 1. When combining fenofibrate with statins, it is essential to monitor for potential side effects, particularly muscle pain and liver function abnormalities, as the risk of muscle-related side effects increases with combination therapy. 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 fenofibrate in patients with severe hypertriglyceridemia, defined as triglycerides above 500 mg/dL, as part of a comprehensive treatment plan 1. Some key points to consider when using fenofibrate with statins include:

• Typical fenofibrate dosing ranges from 48-145 mg daily, with the specific dose depending on the formulation used.
• Regular blood tests to check liver enzymes, kidney function, and creatine kinase levels are recommended, typically at baseline, 12 weeks after starting therapy, and periodically thereafter.
• Fenofibrate works differently than statins by activating peroxisome proliferator-activated receptor alpha (PPAR-α), which increases the breakdown of triglyceride-rich particles and reduces triglyceride production in the liver.
• The combination of fenofibrate and statins is particularly effective for patients with mixed dyslipidemia (elevated LDL cholesterol and triglycerides). It is crucial to evaluate the patient's renal status before initiating fenofibrate, as it should not be used in patients with moderate or severe renal impairment, defined as eGFR <30 mL/min per 1.73 m2, and the dose should not exceed 54 mg/day if eGFR is between 30 and 59 mL/min per 1.73 m2 1.

From the FDA Drug Label

The effects of fenofibrate on serum triglycerides were studied in two randomized, double-blind, placebo-controlled clinical trials of 147 hypertriglyceridemic patients Fenofibrate tablets are indicated as adjunctive therapy to diet to reduce elevated low-density lipoprotein cholesterol (LDL-C), total cholesterol (Total-C), Triglycerides and apolipoprotein B (Apo B), and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia. Fenofibrate tablets are also indicated as adjunctive therapy to diet for treatment of adult patients with severe hypertriglyceridemia.

Fenofibrate can be used to control severely elevated triglycerides, specifically hypertriglyceridemia.

• It is indicated as adjunctive therapy to diet for the treatment of adult patients with severe hypertriglyceridemia.
• The effects of fenofibrate on serum triglycerides were studied in clinical trials, which showed that fenofibrate decreased primarily very low density lipoprotein (VLDL) triglycerides and VLDL cholesterol. However, there is no direct information in the provided drug labels about adding fenofibrate to HMG-CoA reductase inhibitors (statins) to control severely elevated triglycerides. Therefore, no conclusion can be drawn about the safety and efficacy of this combination for this specific use. 2 2 2

From the Research

Efficacy of Fenofibrate in Controlling Hypertriglyceridemia

• Fenofibrate can be effective in reducing triglyceride levels in patients with hypertriglyceridemia, with studies showing a significant reduction in triglyceride levels when used as monotherapy or in combination with other lipid-lowering agents 3, 4, 5, 6.
• The addition of fenofibrate to statin therapy has been shown to improve lipid profiles, particularly in patients with elevated triglycerides despite receiving statin treatment 4, 5, 6.
• Studies have demonstrated that fenofibrate can reduce triglyceride levels by 17.5% to 60.8% when used in combination with other agents or as monotherapy 3, 4, 6.

Safety of Fenofibrate in Combination with Statins

• The safety profile of fenofibrate when used in combination with statins has been evaluated in several studies, with no significant increase in adverse events reported 4, 5, 6.
• However, it is essential to monitor patients for potential side effects, such as muscle damage or elevated liver enzymes, when using fenofibrate in combination with statins 4, 5.

Clinical Implications

• Fenofibrate may be a useful treatment option for patients with hypertriglyceridemia who have not responded to statin therapy alone 4, 5, 6.
• The addition of fenofibrate to statin therapy may be particularly beneficial in patients with atherogenic dyslipidemia, as it can help improve lipid profiles and reduce cardiovascular risk 5, 7.
• Further studies are needed to fully evaluate the efficacy and safety of fenofibrate in combination with statins for the treatment of hypertriglyceridemia 7.