DALLAS — Expectations were high for a big positive result in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, the largest-ever randomized prospective trial of cardiovascular intervention in type 2 diabetes.
Many on hand for the presentation of the FIELD results at the annual scientific sessions of the American Heart Association anticipated outcomes so favorable as to lift fenofibrate into the realm of first-line therapy in diabetic patients, joining the statins.
So when FIELD principal investigator Dr. Anthony Keech announced the study had failed to meet its primary end point, the fall was a hard one. Within hours the stock market knocked 7.3% off the value of Abbott Laboratories shares.
“What a shocker,” Dr. Prakash C. Deedwania said in an interview. “The question after FIELD isn't any longer whether there should be increased fenofibrate use in patients with diabetes, it's whether there's any role for fenofibrate at all.”
FIELD involved 9,795 patients with type 2 diabetes who were randomized in double-blind fashion to 200 mg fenofibrate daily or placebo. None were on statin therapy at baseline. After 5 years, the combined primary end point of nonfatal MI or death due to coronary heart disease (CHD) had occurred in 5.2% of patients on fenofibrate and 5.9% on placebo, a nonsignificant 11% reduction in relative risk. While nonfatal MIs were reduced by 24% in the fenofibrate group, CHD mortality increased by a nonsignificant 19%, said Dr. Keech, professor of medicine at the University of Sydney.
He termed the FIELD results “mixed.” Bright spots included the positive secondary findings of a 21% reduction in coronary revascularization and an 11% reduction in total cardiovascular events, from 13.9% with placebo to 12.5%. For one additional cardiovascular event to be prevented, 70 patients would need to receive fenofibrate for 5 years.
The fenofibrate group also had significantly reduced albuminuria progression, fewer amputations, and less need for laser surgery for retinopathy. But Dr. Deedwania said what really matters in a very-high-risk population such as diabetic patients is whether lives are saved, and fenofibrate failed in this regard.
He shrugged off the improvement in diabetic end points. “That's not why you use the fibrates. We have better drugs for that: the PPAR [peroxisome proliferator-activated receptor] agonists,” said Dr. Deedwania, professor of medicine and chief of the cardiology division for the University of California, San Francisco, Fresno Program.
A key factor in the failure to meet the primary study end point was that the landmark Heart Protection Study reported results midway through FIELD. In response, 17% in the placebo group were put on a statin by their physician, a rate more than twice as high as in the fenofibrate arm. That change clearly played a major role in the loss of fenofibrate's expected benefit, according to Dr. Ginsberg, professor of medicine and head of the division of preventive medicine and nutrition at Columbia University, New York.
FIELD was funded by Laboratories Fournier and the National Health and Medical Research Council of Australia.
Catherine Hackett