Fenofibrates’ Complicated History in Cardiovascular Protective Care, With John Osborne, MD, PhD

Although fenofibrates have had a long history of failed clinical trials with no data to back up their indication, they are still being prescribed to millions of patients nationwide every year to lower cardiovascular event risk.1

Fenofibrates have been prescribed alongside statins for years, despite having no evidence to support this. In recent years, the US Food and Drug Administration (FDA) has reversed its approval for this indication and adjusted the drug’s label to reflect its lack of efficacy. However, 11 million fenofibrate prescriptions were written in 2023 alone, meaning almost 60% of patients are taking medications with no protective effects and possible health risks.1

The editorial team at HCPLive met with John Osborne, MD, PhD, chief medical officer at ClearCardio LLC and immediate past chief executive officer of Metroplex Cardiology and State of the Heart Cardiology, to discuss the ongoing use of these ineffective drugs. Osborne spoke on the history of fenofibrates’ misguided FDA approval and what can be done to spread awareness about its reversal.

“The two trials that were done with fenofibrates – one was the FIELD trial, and then after that was the ACCORD trial,” Osborne told HCPLive. “These trials did include women, although proportionally, the numbers were small. And interestingly, neither of these trials showed benefit. They didn’t show cardiovascular risk reduction, stroke reduction, cardiovascular death reduction, or mortality reduction. We actually saw harm for women. Despite that, the drug was kept on the market.”

Fenofibrates were initially approved for cardiovascular disease risk after a set of trials, FIELD (2005) and ACCORD (2010). Both were randomized, comparing fenofibrate to placebo and standard of care, respectively. FIELD was a multinational randomized controlled trial enrolling 9795 patients aged 50-75 years with type 2 diabetes mellitus (T2DM) and not on statin therapy at study entry. Patients would undergo a placebo and fenofibrate run-in phase, after which they would be randomly assigned to either micronized fenofibrate 200 mg daily (n = 4895) or matching placebo (n = 4900).1,2

Ultimately, investigators for FIELD found that fenofibrate treatment did not significantly reduce the risk of the study’s primary outcome of coronary events. Some evidence did support fenofibrate’s potential in reducing total cardiovascular events, as patients in that arm exhibited fewer non-fatal myocardial infarctions and revascularizations.2

The ACCORD study, meanwhile, saw 5518 patients assigned to either fenofibrate plus simvastatin (n = 2765) or placebo plus simvastatin (n = 2753). Patients were followed up for 4.7 years for the primary outcome – first occurrence of a major adverse cardiovascular event – and 5 years for total mortality rates. By the second follow-up, the annual rate of this primary outcome was 2.2% among patients receiving fenofibrates, compared to 2.4% in the placebo group (HR fenofibrates, 0.92; 95% CI, 0.79 to 1.08; P = .32). Investigators determined that patient sex was the only subgroup demonstrating an interaction, with women exhibiting a 9.1% rate in the fenofibrate group versus 6.6% in the placebo group (P = .01).3

Investigators ultimately declared ACCORD a failure, as the combination of fenofibrate plus simvastatin did not reduce cardiovascular disease rates versus simvastatin alone. This evidence would form the groundwork for the recent PROMINENT study, which supplied the momentum for the FDA’s recent decisions to change the label.3

Osborne also discussed the next steps for fenofibrate prescriptions, including how clinicians can approach patients and colleagues with these data regarding their ineffectiveness. Osborne stressed citing recent scientific evidence and maintaining a clinical tone rather than revisiting the somewhat charged history of the issue, particularly given the current climate of distrust towards medicine in general.

“I think the best way to share this with patients is to be science-based, evidence-based, and to say that there is no data showing fibrates reduce cardiovascular events,” Osborne said. “That’s a great place to start because it’s new, it’s contemporary. You don’t have to rehash all the 20 years’ worth of the unfortunate and unsuccessful fibrate trials. Here, one can point to more recent contemporary analyses of those trials.”

Editors’ Note: Osborne reports no relevant disclosures.

References

1. Osborne J. Millions are Taking a Drug that Falls Short of its Promise to Lower Risk of Heart Attack. MedCity News. September 18, 2024. Accessed January 7, 2026. https://medcitynews.com/2024/09/millions-are-taking-a-drug-that-falls-short-of-its-promise-to-lower-risk-of-heart-attack/

2. Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366(9500):1849-1861. doi:10.1016/S0140-6736(05)67667-2

3. Bailey K, Gohdes D, Haffner S, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. NEJM. 2010;362(17):1563-1574. doi:10.1056/nejmoa1001282