Adding fenofibrate to statin therapy fails to reduce cardiovascular events in patients with type 2 diabetes, according to results of the first trial to evaluate combination therapy presented at the 59th annual scientific session of the American College of Cardiology.

“I think that combination use is very limited. In this study we did not reduce the composite end point, and physicians and their patients are going to have to decide what they are going to do,” said lead investigator Henry N. Ginsburg, MD, Irving Professor of Medicine and director, Irving Institute for Clinical and Translational Research, Columbia University College of Physicians and Surgeons, New York, N.Y. He added that the results suggest that fenofibrate be used only in patients with significantly elevated triglycerides.

Because patients with type 2 diabetes are at high risk for cardiovascular disease and events, it was hoped that combination lipid treatment would lower risk and improve outcomes better than statin therapy to lower low-density lipoprotein (LDL) alone.

“I think there is increased pressure on physicians from a number of sources to consider more treatment for residual risk, particularly lowering triglycerides and raising HDL, and I think this trial shows there is no evidence for that,” Dr. Ginsburg said. “The use of fenofibrate needs to be reassessed.”

ACCORD trial design

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial included 5,518 patients with type 2 diabetes from 77 centers in the United States and Canada. All patients had either pre-existing cardiovascular disease or 2 or more cardiovascular risk factors, and 36.5% had experienced a cardiovascular event before entering the trial. The mean age of study patients was 62.3 years, they had had diabetes for a median of 9 years, and the median hemoglobin A1c at study entry was 8.1%.

“One potential criticism of ACCORD might be that we did not design the trial to look at a very dyslipidemic population,” Dr. Ginsburg said. At baseline, the median low-density lipoprotein (LDL) level was 100.6 mg/dL, the mean high-density lipoprotein (HDL) level was 38.1 mg/dL, and the median triglyceride level was 162 mg/dL.

All patients received simvastatin and were randomly assigned to receive either a starting dose of fenofibrate 160 mg daily or placebo. The fenofibrate dose was modified throughout the trial according to patients’ estimated glomerular filtration rate. Patients were followed a mean of 4.7 years, and the primary outcome measure was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The annual rate of the primary outcome measure was 2.2% for patients taking fenofibrate and 2.4% for patients taking placebo. Furthermore, there was no difference between the groups in rates of cardiovascular death, total mortality, fatal stroke, need for revascularization, or hospitalization for heart failure.

Combination may harm women

The rate of the primary outcome measure was significantly increased among women receiving fenofibrate (9.1%) compared with those taking placebo (6.6%). The rate of events among men was 11.2% for those taking fenofibrate and 13.3% for those taking placebo.

There was a nonsignificant trend toward better outcomes with fenofibrate for patients who had a baseline triglyceride level in the highest third, or 204 mg/dL or greater, combined with an HDL level in the lowest third, or 34 mg/dL or less. For these patients the primary outcome rate was 12.4% in the fenofibrate group and 17.3% in the placebo group.

Dr. Ginsburg said that there was no evidence that fenofibrate increases plasma statin concentrations, which has been previously found with gemfibrozil treatment with an associated increased risk of myositis and rhabdomyolysis. In ACCORD, there was also no difference between treatment groups in the incidence of end-stage renal disease or the need for dialysis, and there was a reduction in microalbuminuria and macroalbuminuria in patients in the fenofibrate group.

MAUDE CAMPBELL is a freelance writer based in the Greater Cleveland area.

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By: Maude Campbell
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