After the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: implications for fenofibrate.
The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study provides an extensive evidence base for the efficacy and tolerability of fenofibrate treatment in patients with type 2 diabetes mellitus, predominantly in a primary prevention setting. The FIELD study did not show a significant effect with fenofibrate on the primary end point, coronary artery disease death or nonfatal myocardial infarction (p = 0.16). Treatment with fenofibrate did reduce all cardiovascular disease (CVD) events, the secondary end point (by 11%, p = 0.035). The primary end point was reduced by the same percentage. The modest percent reduction in the primary and secondary end points is probably a result of a number of study confounders, notably an excess of statin drop-in therapy and disproportionate treatment with other drugs for CVD prevention in the placebo arm. Estimates of relative risk reduction used by the FIELD investigators to equalize the use of statins in the fenofibrate and placebo groups suggest a true benefit of treatment on reduction of CVD events of 17%-21%. There was no excess of elevated serum liver enzymes and no cases of rhabdomyolysis in patients receiving both fenofibrate and a statin. Prevention of microvascular disease, specifically, reduction in the rate of laser treatment for retinopathy (by 30%, p = 0.0003), progression of albuminuria (p = 0.002), and nontraumatic amputations (by 38%, p = 0.011), may well be the most innovative finding of the FIELD study, especially in view of the current lack of effective preventative treatments for diabetic retinopathy and the need for additional treatments that slow the progression of diabetic nephropathy. These findings also give impetus to investigate mechanisms by which fenofibrate and peroxisome proliferator-activated receptor-alpha activation may protect the endothelium of small blood vessels in patients with type 2 diabetes.
Sacks
Frank M
FM
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. fsacks@hsph.harvard.edu
D000924:Anticholesteremic Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D011345:Fenofibrate / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D047493:PPAR alpha / Q000627:therapeutic use; D011322:Primary Prevention; D012306:Risk; D018570:Risk Assessment
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D011345:Fenofibrate