Treatment with fenofibric acid "may not" lower the risk of myocardial infarction or stroke in patients treated with the cholesterol-lowering medication, information that is being added to the drug’s label, the Food and Drug Administration announced on Nov. 9.
The FDA statement and decision to make the labeling change are based on the agency’s review of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) lipid trial, which showed no significant differences in the risk of major adverse cardiac events between patients treated with fenofibrate and simvastatin and those treated with simvastatin alone.
Data from the ACCORD lipid trial have been added to the drug label’s "Important Limitations of Use" and "Warnings and Precautions" sections, and to the medication guide given to patients with each prescription.
"Health care professionals should consider the benefits and risks of Trilipix when deciding to prescribe the drug to patients," the FDA cautioned in its statement, and physicians should encourage their patients to read the medication guide.
At a meeting of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee earlier this year, the panel was divided over how the ACCORD lipid results should affect the drugs labeling and the approved indication for use with a statin. Of the 13 panel members, 6 agreed that the main findings of ACCORD should be added to the drug’s label, while 4 said that the co-administration indication should be withdrawn. The remaining three panelists said that marketing should continue with no label changes.
Fenofibric acid, a peroxisome proliferator receptor-alpha activator marketed as Trilipix by Abbott Laboratories, was approved in 2008, for use with a statin to reduce triglycerides and increase HDL cholesterol in patients with mixed dyslipidemia and coronary heart disease or a CHD risk equivalent who are on optimal statin therapy to achieve their LDL cholesterol goal. It is also indicated as monotherapy to reduce triglycerides in patients with severe hypertriglyceridemia; as monotherapy to reduce elevated LDL cholesterol levels, total-C cholesterol, triglycerides, and apolipoprotein-B, and to increase HDL cholesterol levels in patients with primary hyperlipidemia or mixed dyslipidemia.
In the ACCORD lipid study, patients were treated with simvastatin for 4 weeks and were then randomized to continue treatment with simvastatin and placebo (2,753 patients) or simvastatin and fenofibrate (2,765 patients).
Over a mean follow-up of 4.7 years, the risk of major adverse cardiovascular events (nonfatal MI, nonfatal stroke, and death from cardiovascular disease) was 8% lower among patients on the combination, but the difference was not statistically significant. Among men, the risk was reduced by 18% among those on the combination, compared with those on simvastatin alone.
Among women, however, the risk of major adverse cardiovascular events was 38% greater among those on the combination, compared with those on placebo.
That gender effect was not seen in another large randomized controlled clinical trial comparing fenofibrate to placebo, so "the clinical significance of this subgroup finding is unclear," the FDA statement noted.
But "the study results also raised the hypothesis that a subgroup of patients with high triglycerides and low high-density lipoprotein cholesterol may experience some reduction in the risk of MACE [major adverse cardiovascular events] from the combination therapy vs. simvastatin monotherapy," the agency noted.
The FDA will require Abbott to conduct a randomized, double-blind, placebo-controlled clinical trial to evaluate whether combination treatment with fenofibrate plus a statin significantly reduces the rate of MACE in men and women who are at their LDL cholesterol goal on statin therapy but have residually high triglycerides and low HDL cholesterol.
Serious adverse events associated with Trilipix should be reported to the FDA’s MedWatch program online or at 800-332-1088.