From the Guidelines
Fenofibrate should not be used as a first-line treatment for patients with dyslipidemia, but rather considered for patients with high triglycerides and low HDL cholesterol, especially those with type 2 diabetes or metabolic syndrome, due to its potential benefits in reducing cardiovascular risk. The FIELD study 1 demonstrated a relative risk reduction of 11% in coronary heart disease death and non-fatal MI, although this did not reach statistical significance. However, fenofibrate therapy was associated with a significant reduction in non-fatal MI and total cardiovascular events. The study also highlighted the importance of considering baseline dyslipidemia and potential confounders, such as statin use and homocysteine levels, when interpreting the results.
Key points to consider when prescribing fenofibrate include:
- Typical starting dose: 48-145 mg daily, with dosage adjustments based on lipid levels and kidney function
- Common side effects: digestive issues, muscle pain, and potential liver enzyme elevations
- Regular monitoring of liver enzymes and kidney function is necessary, with dose adjustments required for patients with renal impairment
- Fenofibrate should not be used in patients with severe liver disease, gallbladder disease, or those taking certain statins due to increased risk of muscle damage
- Improvement in lipid profiles typically occurs within 2-4 weeks of starting therapy, with maximum effects seen after 6-8 weeks of treatment
The American College of Cardiology guidelines 1 also support the use of fibrates, such as fenofibrate, as an adjunctive therapy for patients with high triglycerides and low HDL cholesterol, especially in combination with statins. However, the evidence base for fibrate therapy is not as strong as that for statins, and therefore, fenofibrate should be used judiciously and with careful consideration of the individual patient's risk factors and medical history.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Fenofibrate Overview
- Fenofibrate is a fibric acid derivative used to treat primary hypercholesterolaemia, mixed dyslipidaemia, and hypertriglyceridaemia in adults who have not responded to nonpharmacological measures 2.
- Its lipid-modifying effects are mediated by activation of peroxisome proliferator-activated receptor-alpha, and it also has nonlipid (pleiotropic) effects, such as reducing fibrinogen, C-reactive protein, and uric acid levels, and improving flow-mediated dilatation 2, 3, 4.
Lipid-Modifying Effects
- Fenofibrate improves lipid levels, particularly triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) levels, in patients with primary dyslipidaemia 2, 3, 4.
- It is particularly well-suited for use in atherogenic dyslipidaemia, characterized by high TG levels, low HDL-C levels, and small, dense low-density lipoprotein (LDL) particles, which is commonly seen in patients with the metabolic syndrome and type 2 diabetes mellitus 2, 3, 4.
- Combination therapy with a statin or ezetimibe generally improves the lipid profile to a greater extent than monotherapy with either agent in patients with dyslipidaemia and/or type 2 diabetes mellitus or the metabolic syndrome 2, 4.
Cardiovascular Outcomes
- Fenofibrate did not reduce the risk of coronary heart disease events to a greater extent than placebo in patients with type 2 diabetes in the FIELD trial, but it did reduce the risk of total cardiovascular disease events, primarily through the prevention of non-fatal myocardial infarction and coronary revascularisation 2, 3, 4.
- Subgroup analyses revealed significant reductions in total cardiovascular disease events and coronary heart disease events in patients with no previous cardiovascular disease, suggesting a potential role for primary prevention with fenofibrate in patients with early type 2 diabetes 2.
- Fenofibrate also slowed the progression of diabetic retinopathy in the ACCORD trial 3, 4.
Comparison with Other Treatments
- A head-to-head comparison of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia found that fenofibrate had substantially better effects on lipoprotein and metabolic profiles, including decreasing non-HDL cholesterol and triglycerides/HDL cholesterol, and increasing HDL cholesterol and apolipoprotein AI 5.
- Fenofibrate therapy also decreased fasting insulin and increased plasma adiponectin and insulin sensitivity compared to omega-3 fatty acids 5.