Fibrates after the FIELD study: Some answers, more questions

Fibrates have a long history in cardiovascular disease. These drugs raise high-density lipoprotein (HDL)-cholesterol, reduce triglycerides and improve small dense low-density lipoprotein (LDL) so would be expected to have large effects in type 2 diabetes, where this is the typical lipid profile. The general trial results with these agents have been confusing, with varying cardiovascular benefits. The Fenofibrate Intervention and Endpoint Lowering in Diabetes (FIELD) study recruited a low-risk population with a lipid profile that would be more usually treated with a statin. FIELD showed a non-significant 11% reduction (p = 0.16) in the primary end point of coronary events and a significant 11% benefit on the secondary end point of cardiovascular events and procedures (p = 0.04). Most of the benefits were seen in primary prevention and non-fatal myocardial events. Fenofibrate had little effect on HDL-C; the effects of the trial are consistent with the LDL-C reducing potential of this drug. FIELD, because of unequal statin drop-in, gives little evidence on statin-fibrate combination therapy but does reinforce the available data on the safety of fenofibrate-statin combination therapy. In addition, fenofibrate showed possible benefits on microvascular disease end points, including albuminuria and retinopathy. On current data fenofibrate and gemfibrozil seem to be reasonable second-line agents in type 2 diabetes or secondary prevention with low HDL-C, respectively, based on outcome evidence. In combination therapy, drug-specific safety considerations will affect the exact choice of agent, especially in combination with statins, but the efficacy of combination therapy still requires validation in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.