Title: Fenofibrate Intervention and Event Lowering in Diabetes (FIELD)
Year Presented: 2005
Year Published 2005
Summary Posted: 11/14/2005
Writer: Ms. Sabina A. Murphy

Author Disclosure: Research Grants: Astra, Aventis, Boston Scientific, Bristol Myers Squibb, COR Therapeutics, DVI Guidant, Eli Lilly, Genentech, Merck, Millennium Pharmaceuticals, Pfizer, SmithKline Beecham, Sonus, NIH, Percusurge, Pharmadigm, Point Biomedical, TIMI 3 Systems.
Reviewer: C. Michael Gibson, M.D., F.A.C.C.
Author Disclosure: Research/Research Grants: Portola Pharmaceuticals, Inc., Significant (>= $10,000); Research/Research Grants: Fold Rx, Significant (>= $10,000); Consultant/Consulting Fees/Honoraria: Schering Plough Corp., Modest (< $10,000); Research/Research Grants: Briston Meyers Squibb, Significant (>= $10,000); Research/Research Grants: Baxter Corp., Significant (>= $10,000); Research/Research Grants: INO Therapeutics Inc., Significant (>= $10,000); Consultant/Consulting Fees/Honoraria: PDL Pharmaceuticals, Modest (< $10,000); Consultant/Consulting Fees/Honoraria: Angel Medical Systems, Significant (>= $10,000); Ownership/Partnership/Principal: Healthmarx Inc. (spouse), Significant (>= $10,000); Speaker/Speaker’s Bureau: Genentech, Inc., Modest (< $10,000); Consultant/Consulting Fees/Honoraria: Bayer Corp., Modest (< $10,000); Research/Research Grants: Nuvelo, Inc., Significant (>= $10,000); Research/Research Grants: Sanofi-Aventis, Significant (>= $10,000); Consultant/Consulting Fees/Honoraria: Archemix Corp., Significant (>= $10,000); Consultant/Consulting Fees/Honoraria: timi3 Systems, Inc., Modest (< $10,000); Consultant/Consulting Fees/Honoraria: Momenta Pharmaceuticals, Inc., Modest (< $10,000); Consultant/Consulting Fees/Honoraria: Aventis Pharmaceutcals, Modest (< $10,000); Research/Research Grants: Archemix Corp., Significant (>= $10,000); Consultant/Consulting Fees/Honoraria: Biogen IDEC, Modest (< $10,000); Consultant/Consulting Fees/Honoraria: Portaola Pharmaceuticals, Significant (>= $10,000); Consultant/Consulting Fees/Honoraria: Ascenta Therapeutics, Inc., Modest (< $10,000); Research/Research Grants: Kai Pharmaceuticals, Significant (>= $10,000); Research/Research Grants: Abbott Corporation, Significant (>= $10,000); Consultant/Consulting Fees/Honoraria: Atrium Medical Corporation, Significant (>= $10,000); Consultant/Consulting Fees/Honoraria: The Medicines Company, Significant (>= $10,000); Research/Research Grants: Point Biomedical Corp., Significant (>= $10,000); Research/Research Grants: Fold Rx, Inc., Significant (>= $10,000); Research/Research Grants: Eli Lilly Corp., Significant (>= $10,000); Research/Research Grants: CardioKinetix, Significant (>= $10,000); Consultant/Consulting Fees/Honoraria: Heartscape Technologies, Significant (>= $10,000); Research/Research Grants: Astra Zeneca, Significant (>= $10,000); Royalty Income: Pocket Medicine, Modest (< $10,000); Speaker/Speaker’s Bureau: Glaxo Smith Kline, Modest (< $10,000); Speaker/Speaker’s Bureau: The Medicines Company, Modest (< $10,000); Speaker/Speaker’s Bureau: Schering Plough Corp., Significant (>= $10,000); Research/Research Grants: Novartis Corp., Significant (>= $10,000); Research/Research Grants: Genentch Inc., Significant (>= $10,000); Research/Research Grants: Heartscape Technologies, Significant (>= $10,000); Research/Research Grants: Schering Plough Corp., Significant (>= $10,000); Royalty Income: UpToDate in Cardiovascular Medicine, Modest (< $10,000)

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.
Drugs/Procedures Used
Following a 6 week run-in phase, patients were randomized in a double blind manner to fenofibrate (200 mg per day; n=4895) or placebo (n=4900). 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 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%, hazard ratio [HR] 0.47, 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 coronary heart disease death or non-fatal MI (hazard ratio [HR] 0.89, 95% CI 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 non-fatal 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).
Interpretation
Among patients with diabetes at risk for coronary heart disease, treatment with fenofibrate was not associated with a difference in the primary composite endpoint of coronary heart disease death or non-fatal MI compared with placebo at 5 year follow-up.

While the primary endpoint of CHD death or non-fatal MI did not differ by treatment group, several secondary endpoints were lower in the fenofibrate group, including non-fatal 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. The upcoming ACCORD trial will evaluate treatment with fenofibrate compared with placebo in diabetic patients treated with simvastatin, which will provide a more definitive answer of the benefit of fenofibrate in the setting of statin therapy.
Conditions
• Diabetes mellitus

Therapies
• Lipid-lowering agent

Study Design
Placebo controlled. Randomized. Blinded.

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

Primary Endpoints
Composite of coronary heart disease death or non-fatal MI
Secondary Endpoints
Total cardiovascular disease (CVD) events, CVD deaths, total mortality, total stroke, nonhemorrhagic stroke, coronary revascularization, carotid revascularization
Patient Population
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 screeing, plasma creatinine >130 µmol/L
References: 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.