Fenofibrate Intervention and Event Lowering in Diabetes - FIELD

Description:

The goal of the trial was to evaluate treatment with fenofibrate compared with placebo among patients with diabetes at risk for coronary heart disease (CHD).

Study Design

Patients Screened: 13,900
Patients Enrolled: 9,795
Mean Follow Up: 5 years
Mean Patient Age: Mean age 62 years
Female: 37%

Patient Populations:

  • Age 50-75 years
  • Type 2 diabetes diagnosed after age 35 years
  • No clear indication for cholesterol-lowering therapy at baseline (total cholesterol 116-251 mg/dl, plus either total cholesterol to HDL ratio ≥4.0 or triglyceride >88.6 mg/dl)

Exclusions:

  • Triglyceride >443 mg/dl
  • Treatment with lipid-lowering agent at screening
  • Plasma creatinine >130 µmol/L

Primary Endpoints:

  • Composite of CHD death or nonfatal MI

Secondary Endpoints:

  • Total cardiovascular disease events
  • Cardiovascular disease deaths
  • Total mortality
  • Total stroke
  • Nonhemorrhagic stroke
  • Coronary revascularization
  • Carotid revascularization

Drug/Procedures Used:

Following a 6-week run-in phase, patients were randomized in a double-blind manner to fenofibrate (200 mg per day; n = 4,895) or placebo (n = 4,900). Statin and other lipid-lowering medications were allowed at any time after randomization.

Principal Findings:

Median duration of diabetes at baseline was 5 years. Median glycated hemoglobin (HbA1c) was 6.9% at baseline in both groups. Diabetes was managed by diet alone in 26% of patients, and with insulin in 14% of patients. Prior cardiovascular disease was present in 22% of patients. Use of other lipid-lowering medications, or "drop-in" therapy, was more frequent in the placebo group (17% vs. 8%, p < 0.0001), with statins as the lipid-lowering medication used in 94% of these patients.

There was no difference in the primary composite endpoint of CHD death or nonfatal myocardial infarction (MI) (hazard ratio [HR] 0.89, 95% confidence interval 0.75-1.05, p = 0.16). The secondary composite endpoint of total cardiovascular disease events was lower in the fenofibrate group (12.5% vs. 13.9%, p = 0.035), due primarily to a reduction in nonfatal MI (HR 0.76, p = 0.01) and coronary revascularization (5.9% vs. 7.4%, p = 0.004). There was no difference in CHD death (HR 1.19, p = 0.2), total mortality (7.3% vs. 6.6%, p = 0.18), total stroke (3.2% vs. 3.6%, p = 0.36), or nonhemorrhagic stroke (2.9% vs. 3.2%, p = 0.43). Hospitalization for unstable angina occurred less frequently in the fenofibrate group (4.3% vs. 5.1%, p = 0.04).

Total cardiovascular events were reduced in women assigned to fenofibrate (HR 0.80, p = 0.04) and nonsignificantly reduced in men assigned to fenofibrate (HR 0.92, p = 0.2); however, there was no evidence for treatment interaction by gender (p > 0.3).

Interpretation:

Among patients with diabetes at risk for CHD, treatment with fenofibrate was not associated with a difference in the primary composite endpoint of CHD death or nonfatal MI compared with placebo at 5-year follow-up.

While the primary endpoint of CHD death or nonfatal MI did not differ by treatment group, several secondary endpoints were lower in the fenofibrate group, including nonfatal MI and revascularization. Patients in the placebo group were more frequently treated with other lipid-lowering therapy, predominantly statins, during the 5-year follow-up, which may have attenuated any treatment effect differences between the fenofibrate and placebo groups.

There was a suggestion of enhanced benefit among women; however, the ACCORD Lipid trial, which was negative overall, found enhanced benefit among men.

References:

d’Emden MC, Jenkins AJ, Li L, et al. Favourable effects of fenofibrate on lipids and cardiovascular disease in women with type 2 diabetes: results from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetologia 2014;Aug 18:[Epub ahead of print].

The FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005; epub before print.

Presented by Dr. Anthony Keech at the American Heart Association Scientific Session, Dallas, Texas, November 2005.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Diet

Keywords: Fenofibrate, Myocardial Infarction, Stroke, Insulin, Follow-Up Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, Diabetes Mellitus, Type 2, Coronary Disease, Hemoglobin A, Glycosylated, Cholesterol, Hypolipidemic Agents, Diet, Confidence Intervals, Triglycerides, Diabetes Mellitus


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