No greater CV benefit with fenofibrate plus statin vs. statin alone in diabetes

American College of Cardiology 59th Annual Scientific Sessions

ATLANTA – The addition of fenofibrate to simvastatin therapy failed to reduce the rate of fatal and nonfatal cardiovascular events in patients with diabetes, according to new results of the ACCORD Lipid Trial.

The trial investigated patients with well-controlled diabetes who were at high risk for CV disease. In this group, the combined risk for death, nonfatal myocardial infarction or nonfatal stroke — the primary outcome — was similar whether patients were assigned to simvastatin plus fenofibrate or simvastatin plus placebo.

“Overall, the results of the ACCORD Lipid Trial do not support use of combination therapy with fenofibrate and simvastatin to reduce CVD in high-risk patients with type 2 diabetes,” Henry N. Ginsberg, MD, Irving Professor of Medicine an director of the Irving Institute for Clinical and Translational Research at Columbia University College of Physicians and Surgeons, said in a press release.

However, results suggested that patients with the lowest HDL levels and highest triglyceride levels may benefit from combination therapy.

Ginsberg and colleagues studied 5,518 patients with type 2 diabetes and either pre-existing CVD or at least two additional CV risk factors. The researchers randomly assigned patients to simvastatin (Zocor, Merck) plus fenofibrate or simvastatin or simvastatin plus placebo. At baseline, the fenofibrate dose was 160 mg per day, but was later adjusted according to the estimated glomerular filtration rate with use of the abbreviated Modification of Diet in Renal Disease equation because of a rise in serum creatinine levels in some patients receiving this dose.

During a mean follow-up of 4.7 years, the researchers found that combination therapy was safe, but did not significantly reduce the primary outcome of first occurrence of CVD death, nonfatal MI or nonfatal stroke compared with simvastatin alone (annual rate, 2.2% vs. 2.4%; HR=0.92; 95% CI, 0.79-1.08). Combination therapy had no significant effect on secondary outcomes, including individual rates of CVD, nonfatal MI, nonfatal stroke, total mortality, fatal stroke, revascularization or hospitalization for congestive heart failure.

The annual rate of death was 1.5% in the fenofibrate plus simvastatin group compared with 1.6% in the simvastatin alone group (HR=0.91; 95% CI, 0.75-1.10).

Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and suggestion of harm for women (P=.01). The researchers also noted that patients who had triglyceride levels in the top one-third and HDL levels in the bottom one-third at baseline may have benefited from the combination therapy, compared with other participants (P=.057).

“One potential criticism was that we did not design the trial to look at a very dyslipidemic population,” Ginsberg said at press conference today. “The decision was made that we should have a study group from which the results could be widely extrapolated in a general diabetic population.”

This is the first large clinical trial to compare the CV effects of combination therapy with a fibrate plus a statin with statin monotherapy in patients with type 2 diabetes, Ginsberg said.

The ACCORD Lipid Trial data were published simultaneously in the New England Journal of Medicine. – by Katie Kalvaitis

This was a statin trial that went beyond statins, with a combination drug, and it showed no added benefit over the statins alone. This is a very important observation of a drug that has been around and on the market.

– W. Douglas Weaver, MD

Division Head of Cardiovascular Medicine, Director of the Henry Ford Cardiovascular Institute
at Henry Ford Health System and Past President of the ACC

For more information:

• Ginsberg HN. LBCT I. Presented at: American College of Cardiology 59th Annual Scientific Sessions; March 14-16, 2010; Atlanta.

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