Fibrate therapy: Why your heart patients might not benefit as much as you think
Key Takeaways
Fibrates are linked to a reduction in triglyceride levels.
Studies have found that fibrates do not substantially reduce the risk of heart disease and cardiovascular events.
Fibrates have been proven and used to help reduce triglyceride levels for decades.[] They are often prescribed to promote overall cardiovascular health and lower the risk of heart disease. More than one million people with cardiovascular disease risk are being treated off-label with fenofibrate. Studies, however, have not shown that fenofibrates provide greater benefits than statins in reducing the risk of heart health conditions.
Raj Dasgupta, MD, Chief Medical Advisor for Fortune Recommends, explains, “Fibrates mainly lower triglycerides and increase good cholesterol but aren’t as effective at lowering bad cholesterol (LDL). Since LDL is more closely linked to heart disease, the overall impact of fibrates on heart health is smaller compared to other medications like statins.”
In 2015, the United States Food and Drug Administration (FDA) changed indications from the labeling of fenofibrates.[] Prior to 2015, fenofibrates were approved for co-administration with statins for heart health. The FDA stated in 2016 that it changed the indication because the benefits of fenofibrates with statins no longer outweighed the risks.
Understanding fibrate risks
In studies, the use of fibrates with statins has been linked to a range of side effects and risks, including severe health events such as blood clots, liver injury, and adverse kidney events. Additional risks include myopathy, venous thromboembolism, and rhabdomyolysis.
“The main risks include muscle pain, gallstones, and liver problems,” Dr. Dasgupta tells MDLinx. “If used with statins, the risk of muscle and liver issues goes up. Fibrates may also affect kidney function, particularly in people who already have preexisting kidney problems.”
In 2022, the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study found that fibrate therapy was not an effective method of reducing the risk of heart disease over statins.[]
The PROMINENT study tested fibrate therapy with administration to patients with multiple preexisting cardiovascular risk factors, including type 2 diabetes, low HDL cholesterol, and high triglycerides. Study data identified similar risks to those found in earlier studies but did not find any substantial heart health benefit for participants, confirming the FDA’s statement that the fibrates’ benefits do not outweigh the risks.
Look out for possible label changes
Despite the FDA’s label change and findings of multiple studies, fenofibrates are still prescribed for heart health. The nonprofit organization HealthyWomen is advocating for additional label changes in hopes of increasing awareness.[]
In April 2024, HealthyWomen filed a petition urging the FDA to reassess fenofibrate labeling to combat “the widespread misimpression” that fenofibrates, when used alone or along with statins, reduce cardiovascular risk. The petition argues that current labeling allows for the “pervasive, improper utilization of fenofibrates.”
The petition asks for two primary changes: that the FDA update labeling to reflect the most recent benefit and risk data and take further actions to ensure that this information is communicated to practitioners.
Other heart health treatment options
“Statins are the go-to for preventing heart disease because they lower bad cholesterol and reduce heart attack and stroke risk,” Dr. Dasgupta says. Statins are the first-line medication recommended by the American College of Cardiology (ACC).[] Although statins are linked to some risks, such as an increased risk of diabetes, the ACC has stated that the benefits outweigh the risks. In a July 2024 study on predicting atherosclerotic cardiovascular disease, study authors stated, “In this era of available generics, cost-benefit of statins and antihypertensive medication is no longer an issue. And while statins increase the risk of diabetes, the benefit outweighs risk, and using low-dose high-intensity statins with ezetimibe would reduce risk of diabetes.”
Keep in mind, statins aren’t the only treatment option for patients with high triglyceride levels and other heart health risk factors. Dr. Dasgupta explains that newer options, such as proprotein convertase subtilisin/kexin type 9 (PSK9) inhibitors, can sometimes be a great treatment choice.
“Options include prescription fish oil for high triglycerides or newer drugs like PCSK9 inhibitors for people who need more help lowering bad cholesterol,” Dr. Dasgupta says.
Fibrates can be beneficial for some patients. They have been shown to lower triglyceride levels and can be a key part of cholesterol and triglyceride management, Dr. Dasgupta adds. “Fibrates can help people with very high triglycerides, especially those with conditions like diabetes or metabolic syndrome.”
What this means for you
Fibrates are often prescribed off-label to reduce the risk of heart disease. Research, however, does not support this use. Indications and labeling of medication can change with time. It’s a good idea for physicians to stay up to date on the latest approved uses of medications—including off-label uses—and related studies.