What is the role of Fenofibrate in treating high cholesterol?

From the Guidelines

Fenofibrate is a recommended medication for treating high cholesterol, particularly in patients with mixed dyslipidemia, diabetes, or metabolic syndrome, as it can reduce triglycerides by 20-50% and modestly increase HDL levels by 10-20% 1.

Key Points to Consider

• Fenofibrate works by activating peroxisome proliferator-activated receptor alpha (PPAR-alpha), which increases the breakdown of triglyceride-rich particles and reduces their production in the liver.
• Typical dosing ranges from 48 mg to 145 mg once daily, with the specific dose determined by a healthcare provider based on individual patient factors.
• Fenofibrate has less effect on LDL (bad cholesterol) compared to statins, but it can be used in combination with statins to achieve greater reductions in cardiovascular risk, although this combination may increase the risk of myopathy 1.
• Common side effects include digestive issues, muscle pain, and potential liver enzyme elevations, and patients should have regular blood tests to monitor liver function and kidney function while using this medication.
• Fenofibrate should be taken with food to enhance absorption, and it works best when combined with lifestyle modifications like a heart-healthy diet, regular exercise, and smoking cessation.

Important Considerations for Patient Care

• Patients with clinical CVD or over age 40 years with other CVD risk factors should be considered for pharmacological treatment, including fenofibrate, regardless of baseline lipid levels 1.
• The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal MI, or nonfatal stroke, as compared with simvastatin alone, in patients with type 2 diabetes who were at high risk for CVD 1.
• Fenofibrate may be useful for decreasing high triglyceride concentrations and increasing low HDL cholesterol, and can further lower LDL cholesterol when applied together with a statin, but other drugs metabolized through cytochrome P450 should be avoided when this combination is prescribed 1.

From the FDA Drug Label

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.

El papel de Fenofibrato en el tratamiento de la hipercolesterolemia es reducir los niveles elevados de colesterol de lipoproteína de baja densidad (LDL-C), colesterol total, triglicéridos y apolipoproteína B (Apo B), y aumentar los niveles de colesterol de lipoproteína de alta densidad (HDL-C) en pacientes adultos con hipercolesterolemia primaria o dislipidemia mixta. También se utiliza para tratar la hipertrigliceridemia severa en pacientes adultos. 2 2 2

• Indicaciones:
  • Reducir los niveles elevados de LDL-C, colesterol total, triglicéridos y Apo B.
  • Aumentar los niveles de HDL-C.
• Población objetivo: Pacientes adultos con hipercolesterolemia primaria o dislipidemia mixta, y pacientes adultos con hipertrigliceridemia severa.

From the Research

Role of Fenofibrate in Treating High Cholesterol

• Fenofibrate is a fibric acid derivative used to treat high cholesterol and mixed dyslipidemia 3.
• It works by reducing levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and apolipoprotein (apo) B, while increasing levels of high-density lipoprotein cholesterol (HDL-C) and apo A 3.
• Fenofibrate is effective in lowering TG levels and increasing HDL-C levels, with its LDL-C-lowering effect being greater than that of gemfibrozil 3.

Efficacy and Safety of Fenofibrate

• Studies have shown that fenofibrate is effective in reducing TG, TC, and LDL-C levels, and increasing HDL-C levels in patients with dyslipidemias 3, 4.
• Fenofibrate has been found to be well-tolerated, with a low incidence of adverse effects and laboratory abnormalities 3, 5.
• However, fenofibrate therapy has been associated with increases in serum aminotransferase levels, and clinical monitoring of these markers of liver function should be performed regularly 3.

Mechanism of Action

• Fenofibrate has been found to decrease plasma PCSK9 concentrations, which correlates with its LDL cholesterol-lowering effects 6.
• PCSK9 promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its decrease may contribute to the efficacy of fenofibrate in reducing LDL-C levels 6.

Use in Specific Patient Populations

• Fenofibrate has been found to be effective and safe in patients with metabolic syndrome and elevated TG levels 4.
• It has also been found to be effective in reducing plasma lipids and affecting plasma redox status in chronic hemodialysis patients with mild hypertriglyceridemia 7.
• Combination therapy with fenofibrate and a statin has been found to be generally safe and effective for the treatment of combined hyperlipidemia in patients with normal hepatic and renal function 5.