No Benefit in Adding Fenofibrate to Statin for Preventing Cardiovascular Events: Presented at ACC
By Walter Alexander

ATLANTA -- March 15, 2010 -- In the Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Lipid trial, the combination of fenofibrate and simvastatin, compared with simvastatin alone, failed to reduce cardiovascular events in the majority of patients with type 2 diabetes at high risk for cardiovascular disease.

After a mean follow-up of 4.7 years, major cardiovascular events were reported at an annual rate of 2.41% (310 events) in patients receiving a statin plus placebo versus 2.24% in patients receiving a statin plus fenofibrate (hazard ratio [HR] in the fenofibrate group = 0.92; 95% confidence interval [CI], 0.79-1.08; P = .32).

"ACCORD-Lipid does not support use of the combination of fenofibrate and simvastatin compared with simvastatin alone to reduce cardiovascular events," said Henry Ginsberg, MD, College of Physicians & Surgeons, Columbia University, New York, New York, on March 14 here at the 59th Annual Scientific Sessions of the American College of Cardiology (ACC) during a late-breaking presentation.

In the multicentre, double-blinded study, researchers randomised 5,518 patients with type 2 diabetes plus documented cardiovascular disease, evidence of subclinical cardiovascular disease or at least 2 additional cardiovascular risk factors, to receive simvastatin 20 to 40 mg/day plus fenofibrate 54 to 160 mg/day (n = 2,765), or simvastatin plus placebo (n = 2,753).

The primary endpoint was first occurrence of a major cardiovascular event (nonfatal myocardial infarction [MI], nonfatal stroke, or combined risk of cardiovascular death).

Patients had an Hb A1C of >=7.5%; low-density lipoprotein cholesterol (LDL-C) was between 60 and 180 mg/dL; high-density lipoprotein cholesterol (HDL-C) was <55 mg/dL for women and African Americans or <50 mg/dL for all other groups; and triglycerides were <750 mg/dL (untreated) or <400 mg/dL (on a lipid medication).

There were no significant differences between the 2 study groups with respect to any secondary outcome. Annual death rates were 1.5% in the fenofibrate group and 1.6% in the placebo group (HR = 0.91; 95% CI, 0.75-1.10; P = .33).

Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P = .01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of HDL-C (P = .057 for interaction).

Adverse events were similar between groups, with no differences in severe muscle aches/pains, myopathy, myositis, or rhabdomyolysis.

During the ACC press conference, Dr. Ginsberg commented, "I see patients with the worst lipid disorders and the highest riskI add fenofibrate to a statin in those people whose triglycerides are over 200 mg/dL and whose HDL-C is in the mid-thirties. I think that if the general population of physicians who treat patients with diabetes want to accept this subgroup analysis as being meaningful, they might want to expand their use of this drug."

[Presentation title: Effects of Combination Lipid Therapy on Cardiovascular Events in Type 2 Diabetes Mellitus: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial. Late-Breaking Clinical Trials I]