FIELD study: fenofibrate therapy reduced cardiovascular events in Type 2 diabetes

November 14, 2005—Macrovascular and microvascular benefits were found with fenofibrate in the 78% of patients with Type 2 diabetes and no previous cardiovascular disease, and who were statin naïve. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, is the largest intervention study ever conducted in diabetes, and was presented by Dr. Anthony Keech, University of Sydney, Australia at the 2005 Scientific Sessions of the American Heart Association, held in Dallas, Texas from November 13-16. It was published simultaneously as an early online release by The Lancet (DOI:10.1016/S0140-6736(05)67667-2).

“The FIELD study findings indicate that fenofibrate reduces the risk of cardiovascular disease, mainly through the prevention of non-fatal myocardial infarction and coronary revascularizations,” Keech stated.

In this double-blind, randomized, placebo-controlled trial, 9795 patients (50-75 years old with Type 2 diabetes) in Australia, New Zealand and Finland were randomized to fenofibrate 200 mg daily or matching placebo. Physicians could initiate other lipid lowering therapy, and this occurred in 17% of the placebo group and 8% of the fenofibrate group (p<0.0001). Median follow-up was 5 years, with evaluations every 6 months for outcome events and safety assessments.

Key results

Compared to placebo, fenofibrate reduced the primary endpoint by 11% (not significant) and the secondary endpoint by a significant 11% (p=0.035). Further, there was a significant 21% reduction in the need for coronary revascularization (p=0.003). The primary endpoint was coronary events defined as coronary heart disease death or non-fatal MI. The pre-specified secondary endpoint was total cardiovascular events.

Notably, 78% of the patients comprised a primary prevention subgroup without previous cardiovascular events, and significantly larger treatment effects were seen in these patients. Specifically, a 19% reduction in the secondary endpoint of total cardiovascular events (p<0.004), an absolute risk reduction of 2%, with a number needed to treat of 50 patients for 5 years to prevent one cardiovascular event.

More coronary deaths and few other vascular deaths were found in the fenofibrate group, but this was not statistically significant. A nonsignificant increase in total mortality was  also seen in the fenofibrate group.

Regarding microvascular events, a significant reduction in the number of patients developing microalbuminuria or progressing to macroalbuminuria and more frequent regression of albuminuria (p=0.002 for each). Also, a significant 30% reduction in the need for retinal laser treatments was found (3.6% fenofibrate, 5.2% placebo; p=0.0003).

Adjustment for the addition of other lipid-lowering agents in a time-dependent Cox regression analysis showed a 19% risk reduction for coronary heart disease events (p=0.01) and a 15% reduction in total cardiovascular events with fenofibrate compared to placebo.

Fenofibrate was well tolerated alone or in combination with other drugs.

What do the results mean?

Keech stated that “people with Type 2 diabetes have been well represented in other landmark trials of lipid-lowering treatment for the secondary prevention of cardiovascular disease, but what is interesting about the FIELD study is that it shows that fenofibrate treatment can prevent macro- and microvascular complications in people in early stages of Type 2 diabetes with or without dyslipidemia.

The investigators stated in the published article that “FIELD provides information to help guide clinicians on the future use of fenofibrate in patients with Type 2 diabetes. The results are likely to be of particular importance among patients without previous cardiovascular disease and in settings where both the prevention of non-fatal macro-vascular and microvascular complications are judged important.”