From the Guidelines
Fenofibrate should be used to reduce the risk of cardiovascular events in patients with type 2 diabetes, particularly in those without previous cardiovascular disease, as evidenced by the FIELD study 1. The use of fenofibrate, a fibric acid derivative, is primarily focused on managing high cholesterol and triglyceride levels in the blood, which is a significant concern in patients with diabetes. According to the FIELD study 1, fenofibrate therapy was associated with a relative risk reduction of 11% in the primary endpoint of coronary heart disease death and non-fatal MI, although this did not reach statistical significance. However, non-fatal MI was reduced significantly, and total cardiovascular events were also significantly reduced by fenofibrate therapy.
Key Points to Consider
- Fenofibrate is most beneficial in patients with type 2 diabetes without previous cardiovascular disease, as shown by a post hoc analysis of the FIELD study 1.
- The medication can reduce the risk of coronary events in these patients, but its effect in those with previous cardiovascular disease is less clear.
- Fenofibrate therapy was associated with a reduction in total cardiovascular events, including cardiac death, MI, stroke, coronary, and carotid revascularization 1.
- The use of fenofibrate may require careful consideration of its potential effects on homocysteine levels and its interaction with other medications, such as statins.
Clinical Implications
- Fenofibrate should be considered as an adjunctive therapy to statins in patients with type 2 diabetes and high triglyceride levels 1.
- Regular monitoring of lipid levels, liver function, and cardiovascular events is essential in patients taking fenofibrate.
- The medication should be used cautiously in patients with liver or kidney disease, and dose adjustments may be necessary in these cases.
- Patients should be informed about the potential side effects of fenofibrate, including digestive issues and muscle-related side effects when used in combination with statins.
From the FDA Drug Label
Fenofibrate is a peroxisome proliferator-activated receptor (PPAR) alpha agonist indicated as an adjunct to diet: To reduce elevated LDL-C, Total-C, TG and Apo B, and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia. (1.1) For treatment of adult patients with severe hypertriglyceridemia. (1.2)
The use of Fenofibrate is to:
- Reduce elevated LDL-C, Total-C, TG, and Apo B
- Increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia
- Treat adult patients with severe hypertriglyceridemia 2
From the Research
Use of Fenofibrate
Fenofibrate is a fibric acid derivative used in the treatment of various lipid disorders, including:
- Severe hypertriglyceridaemia
- Mixed dyslipidaemia
- Primary hypercholesterolemia
- Hypertriglyceridemia
Mechanism of Action
The lipid-modifying effects of fenofibrate are mediated by the activation of peroxisome proliferator-activated receptor-α 3. Fenofibrate also has nonlipid, pleiotropic effects, such as:
- Reducing levels of fibrinogen, C-reactive protein, and various pro-inflammatory markers
- Improving flow-mediated dilatation
- Promoting a shift from small, dense, atherogenic LDL particles to larger, less dense LDL particles
Clinical Efficacy
Fenofibrate has been shown to:
- Improve the lipid profile, particularly triglyceride and high-density lipoprotein-cholesterol levels 3, 4, 5
- Reduce the risk of some nonfatal macrovascular events and the incidence of certain microvascular outcomes 3
- Decrease the risk of coronary heart disease events in patients with atherogenic dyslipidaemia 3
- Have a uricosuric property, which may be a useful adjunctive attribute 4
Comparison with Other Treatments
Fenofibrate has been compared to other treatments, including:
- Statin monotherapy: fenofibrate tends to improve triglyceride and HDL-C levels to a greater extent, while statins improve LDL-C and total cholesterol levels to a greater extent 3
- Omega-3 fatty acids: fenofibrate has substantially better effects on lipoprotein and metabolic profiles in patients with hypertriglyceridemia 6
Safety and Tolerability
Fenofibrate is generally well tolerated, with a low incidence of adverse effects and laboratory abnormalities 3, 4, 5. However, it can cause:
- Gastrointestinal symptoms
- Cholelithiasis
- Hepatitis
- Myositis
- Rash
- Increases in serum aminotransferase levels, which should be monitored regularly 4