From the Guidelines
Yes, patients can take fenofibrate and statins together, but this combination requires careful monitoring due to an increased risk of muscle problems, as noted in the European guidelines on cardiovascular disease prevention in clinical practice 1. This combination therapy is typically used when a patient has mixed dyslipidemia (high LDL cholesterol and high triglycerides) that doesn't respond adequately to statin therapy alone. Common statin medications include atorvastatin, rosuvastatin, and simvastatin, while fenofibrate is available under brand names like Tricor and Fenoglide. When prescribed together, doctors often start with lower doses of both medications and gradually increase as needed while monitoring for side effects. Some key points to consider when using this combination include:
- Fibrates, particularly fenofibrate, may be useful not only for decreasing high triglyceride concentrations and increasing low HDL cholesterol but can further lower LDL cholesterol when applied together with a statin 1.
- Other drugs metabolized through cytochrome P450 should be avoided when this combination is prescribed 1.
- Fibrates should preferably be taken in the morning and statins in the evening to minimize peak dose concentrations and decrease the risk of myopathy 1.
- Patients have to be instructed about warning symptoms (myalgia) even though these adverse effects are very rare 1.
- Avoiding the addition of gemfibrozil to a statin regimen is advised 1. The most concerning potential side effect is rhabdomyolysis, a rare but serious condition involving muscle breakdown. This combination works effectively because statins primarily lower LDL cholesterol while fenofibrate is particularly effective at reducing triglycerides and increasing HDL (good) cholesterol, providing complementary lipid-lowering effects through different mechanisms of action. Additionally, the ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction suggest that the combination of high-dose statin plus fibrate can increase the risk for severe myopathy, and statin doses should be kept relatively low with this combination 2. However, the most recent and highest quality study, the European guidelines on cardiovascular disease prevention in clinical practice 1, provides the most relevant guidance on this topic.
From the Research
Combination Therapy with Fenofibrate and Statins
- The combination of fenofibrate and statins can be useful for patients with mixed dyslipidemia, as it has been shown to improve lipid profiles and reduce cardiovascular risk 3, 4, 5.
- Large randomized clinical trials have demonstrated that the combined administration of fenofibrate with simvastatin is not associated with a significantly increased incidence of serious adverse events compared with simvastatin monotherapy 3.
- However, the incidence of rhabdomyolysis is slightly increased with fibrate/statin combination compared with monotherapy, although the actual risk is very low 3.
Safety Considerations
- Fenofibrate can increase creatinine and homocysteine serum levels, but the incidence of diabetic nephropathy and thrombotic events was not significantly increased with fenofibrate/simvastatin combination compared with simvastatin monotherapy in some studies 3, 4.
- The combination of fenofibrate and high-intensity statins may have additional benefits, including a lower risk of major adverse cardiac and cerebrovascular events 4.
- Fenofibrate has been shown to be effective and well-tolerated in patients with hypertriglyceridemia and metabolic syndrome, with significant reductions in triglyceride and non-HDL-C levels 6.
Patient-Specific Considerations
- Patients with advanced chronic kidney disease (CKD) may benefit from the combination of fenofibrate and statins, as it has been shown to delay the need for dialysis and reduce cardiovascular risk 4.
- The efficacy and safety of fenofibrate in combination with atorvastatin and ezetimibe have been demonstrated in patients with mixed dyslipidemia, with significant improvements in lipid and non-lipid parameters 5.