Petition asks FDA to revise fenofibrate labeling to emphasize no CV outcome benefits

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Key takeaways:

  • HealthyWomen has filed a petition asking the FDA to require changes to the labeling of fenofibrates.
  • The petition states the labeling does not make clear that fenofibrates do not improve CV outcomes.

Because the science underpinning medicine evolves so quickly, it is not uncommon for some doctors to manage patients based on old evidence that is no longer a best practice; this is called clinical inertia.

Clinical inertia is a powerful force, and sometimes measures such as mandates from regulatory agencies are needed to combat it. This is one reason why there is a petition requesting the FDA to require changes in the labeling of fenofibrates.

Graphical depiction of source quote presented in the article

Fenofibrates lower triglycerides with a modest effect on LDL, and have never been shown to improve CV clinical outcomes. However, the petition filed in April by HealthyWomen, a nonprofit organization dedicated to educating middle-aged women about health, states that current labeling of fenofibrates does not make that clear.

The petition asks the agency to “remedy the widespread misimpression among health care professionals that fenofibrates, when used alone or in combination with statins, reduce cardiovascular risk” because the misimpression has led to “pervasive, improper utilization of fenofibrates” despite evidence from trials such as PROMINENT that fibrates do not improve CV outcomes. On June 19, Amarin, the manufacturer of icosapent ethyl (Vascepa), a pharmaceutical-grade omega-3 fatty acid that lowers triglycerides and has been shown to reduce CV events, filed a comment to the FDA supporting the petition.

Healio spoke with Payal Kohli, MD, FACC, founder and medical director of Cherry Creek Heart in Aurora, Colorado and associate adjunct professor in the division of cardiology at Duke University School of Medicine, who is helping to educate about the petition, about why the labeling of fenofibrates should be changed, why some clinicians remain unaware of the risks and benefits of the drugs and what improved labeling might mean for patients at risk for heart disease and/or pancreatitis.

Healio: What prompted the creation of this petition?

Kohli: In medicine, we are always worried about committing “errors of commission.” For example, we are worried about starting an anticoagulant in an older woman who might fall and have a bleed. But one of the things we don’t worry about, which we should worry about as medical providers, is “errors of omission.” These are things that we are not doing every single day in our office that are not preventing bad outcomes.

An error of omission that we have been doing for over a decade is that we are not using CV risk-reducing medications and we are not using the appropriate clinical application of fibrates. That is one of the reasons we felt compelled to speak up and push the FDA and others to put their stamp on the fact that fibrates do not reduce CV outcomes and should not be used for that particular indication.

Healio: What have been some of the consequences of the current labeling of some of the FDA-approved fenofibrates?

Kohli: The FDA’s label of fenofibrates has evolved over time as new data have come out. In 2015, the agency said fibrates and statins should not be used together, and that fibrates on top of statins do not reduce CV risk further than statins alone. That happened almost a decade ago, and yet, in 2024, we are still seeing that about 50% of health care providers, including cardiologists, still believe that fibrates reduce CV risk.

Under the current label, it is not quite clear that these are not CV risk-reducing medications, even though the data have supported that well. The way the label is written right now is very nebulous. It says you can use the product in patients with hypertriglyceridemia or dyslipidemia — which means elevated triglycerides and low HDL — and you can also use it to reduce the risk for pancreatitis. Because of clinical inertia, providers have said, A equals B and B equals C, therefore A must equal C. So if I am reducing triglycerides, which people think about in the same way as reducing LDL, then I must be reducing CV risk as well. That’s the part that is not clear, and the current label creates confusion around that. It needs to be more clear that the reason that the FDA is asking us to use these medicines is to reduce the risk for pancreatitis, not so much to treat CV risk. That is where many providers are missing the link.

Healio: Why do you think some providers remain unaware that fibrates do not reduce risk for heart attack and stroke?

Kohli: Human behavior is very complex, especially when it comes to application of new science and technology. In the modern day, health care providers are drinking from a fire hydrant of information. The science is evolving so rapidly and keeping up has been tricky, especially for the general practitioner who sees a whole host of different conditions. I think some of this is the lack of knowledge, but a lot of people don’t have the bandwidth to keep up with the science. And some of it is that we are still learning. The PROMINENT trial [showing pemafibrate lowered triglycerides but not CV events] came out less than 2 years ago and gave us new insight into fibrates and their lack of CV risk reduction and potential for harm.

We are also learning that as time goes on, we change our stances on things sometimes. When I was in training, fibrates were embraced. We were writing prescriptions for fibrates pretty regularly for our cardiac patients, even prescribing them with statins despite the risk for drug-drug interactions, because we thought we were doing good. You feel good when you get a patient’s lipid panel back and see a 30% to 50% reduction in triglycerides, because you feel like you’ve done something. So that disconnect where triglycerides are going down and HDL is going up but that doesn’t translate into reducing major adverse CV events is a piece of clinical inertia that has been hard to change. Triglycerides are very different from LDL; we are not treating them to a target, unless we need to get them under 500 mg/dL to reduce risk for pancreatitis. We need to think about risk reduction in a more global sense.

Healio: Do fibrates have a role in patients who are statin-intolerant?

Kohli: They absolutely do. They may even have a role in some patients on statins. This is mainly the case for patients with severe hypertriglyceridemia; those with triglycerides over 500 mg/dL who need that number lowered to reduce the risk for pancreatitis. But for these patients, you also need to think about medications that reduce CV risk. LDL is the main pathway to atherosclerotic CVD, but a parallel pathway is the triglyceride pathway. It identifies people that you may want to treat more aggressively. If triglycerides are over 500 mg/dL, think about using fibrates along with CV risk-reducing medications. If the triglycerides are between 150 mg/dL and 500 mg/dL and the patient is at high risk for CVD or has CVD, then the triglycerides have a target sign on them and identify that the patient should benefit from further CV risk reduction. That could come in the form of icosapent ethyl or obesity medications, which we know reduce triglycerides as well as treat other aspects of metabolic syndrome.

But the one thing I don’t want people to do is to use fibrates as a CV risk reduction medicine, especially if they use fibrates to the detriment of a drug that is actually going to reduce CV risk. We need to think about every patient individually. If we need to use fibrates to lower triglycerides that are over 500 mg/dL, we can (to reduce pancreatitis risk), but we also want to think about layering on top of that a CV risk reduction medication. If someone comes into my office and has CVD and is obese, I am not going to reach for a fibrate, because I know that if I treat the obesity, probably with a GLP-1 receptor agonist that has a label for CV risk reduction, I may also reduce the triglycerides. That way, I can get the weight and the triglycerides down and help with other disease phenomena that occur with obesity. Then I can reevaluate to see if they would benefit from an additional CV risk-reducing medicine or, if their triglycerides are still over 500 mg/dL, from a fibrate.

Healio: If the labeling of FDA-approved fenofibrates is changed per the recommendation of the petition, what are the implications for patients?

Kohli: As a cardiologist, the ultimate privilege is to be able to reduce heart attacks and strokes and make people live longer. We know that heart disease is the leading cause of death in men and women. Preventive cardiologists get our “dopamine hit” not from putting stents in, but from preventing major adverse CV events. The hope with this petition is the ability to have more people take up CV risk reduction medications and to spread the knowledge that this issue is important and should induce behavioral change so people become more thoughtful about their use of fibrates, maybe stopping fibrates in people who don’t need them and using CV risk-reducing medications to change the trajectory of a patient’s disease. We want everyone to stop, take notice and align their clinical behavior with what the evidence has shown.

Healio: Is there anything else you’d like to mention?

Kohli: One of the biggest challenges of being a physician in the modern day is to adapt and keep up with the rapid evolution of science. It is a privilege to have so much great new science in cardiology, but it is important to be continuously changing our practice patterns. If we are practicing in the same way today that we were 5 or 10 years ago, we are making errors of omission. We are missing science, we are missing new data and we are not evolving. I want this to be a wake-up call for medical providers everywhere that we need to be changing our practice patterns every year as the science supports it.


For more information:

Payal Kohli, MD, FACC, can be reached at; X (Twitter): @payalkohlimd.

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