FDA Issues ‘Safety Communication’ on Fenofibrate

The US FDA has issued a safety communication and updated the prescribing information for the cholesterol-lowering agent fenofibric acid (Trilipix, Abbott), stating that the drug may not lower the risk of major cardiovascular events [1]. This is based on data from the ACCORD Lipid trial, in which the combination of fenofibrate plus simvastatin was compared with simvastatin alone in patients with type 2 diabetes mellitus.

The FDA has reviewed this trial as part of its ongoing investigation of the safety and efficacy of fenofibric acid. The agency notes that its review found that there was no significant difference in the risk of experiencing a major adverse cardiac event between the fenofibrate/simvastatin group and the simvastatin-alone group in the trial. In addition, a subgroup analysis showed that relative to treatment in men, there was an increase in the risk for major adverse cardiac events in women receiving the combination therapy vs simvastatin alone. But it adds that the clinical significance of this subgroup finding is unclear.

Based on these results and other clinical trials of similar drugs, the FDA says it has requested Abbott to conduct a clinical trial to evaluate the cardiovascular effects of fenofibric acid in patients at high risk for cardiovascular disease who are already taking statins.

These results from the trial have been added to the product label and to the patient medication guide. The agency says: “Healthcare professionals should consider the benefits and risks of Trilipix when deciding to prescribe the drug.”

These actions follow an FDA advisory panel meeting earlier this year in which the committee recommended that a new trial was needed of fenofibrate in diabetic patients who have met their LDL-cholesterol goal on a statin but still have high triglycerides and low HDL cholesterol.

Fenofibrate was approved in 2008 to be used with a statin to reduce triglycerides and increase HDL cholesterol in diabetic patients with mixed dyslipidemia and coronary disease or at risk of coronary disease who are already on optimal statin therapy to achieve their LDL-cholesterol goal.

Over nearly five years of follow-up in ACCORD, the composite of fatal cardiovascular events, nonfatal MI, and nonfatal stroke was around 11% in both patients randomized to simvastatin plus fenofibrate and patients randomized to simvastatin plus placebo. However, there was a strong trend toward fewer cardiac events in patients with high triglycerides and low HDL cholesterol treated with fenofibrate. In the current safety communication, the FDA refers to this result as “hypothesis raising” and needing confirmation by another trial.

The Europeans seem to have taken a slightly more favorable view of the ACCORD Lipid results. An expert consensus panel from the European Atherosclerosis Society (EAS) recently recommended fibrates as one option for patients with elevated triglycerides and low HDL-cholesterol levels, although it acknowledged that the data were mixed and somewhat controversial.

1.Food and Drug Administration. FDA Drug Safety Communication: Review update of Trilipix (fenofibric acid) and the ACCORD Lipid trial. November 9, 2011. Available here.