Fibrates in the treatment of dyslipidemias--time for a reassessment.

n engl j med 365;6 nejm.org august 11, 2011 481 other risk factors. Yet a substantial risk persists, suggesting that additional lipid-modifying interventions may be needed. High triglyceride levels and low levels of high-density lipoprotein (HDL) cholesterol independently correlate with increased cardiovascular risk, and data from the National Health and Nutrition Examination Survey show that approximately 7% of the U.S. population has combined dyslipidemia of high triglycerides (≥200 mg per deciliter) and low HDL cholesterol (<40 mg per deciliter in men, <50 mg per deciliter in women). However, the clinical benefit of modulating these levels with agents such as niacin, fibrates, or cholesteryl ester transfer protein inhibitors has not been firmly established. Fibrates were introduced more than 35 years ago in Europe, where their regulatory approval was based on favorable changes in the lipid profile, yet there remains considerable controversy regarding their clinical efficacy. Two randomized, placebocontrolled trials of gemfibrozil demonstrated improvements in cardiovascular outcomes,1,2 but subsequent trials of bezafibrate and fenofibrate showed no significant overall cardiovascular benefit over placebo (see Table 1).3-5 The Food and Drug Administration (FDA) first approved fenofibrate (Tricor) in 1993 for severe hypertriglyceridemia. In 1999, fenofibrate was approved for reducing LDL cholesterol, triglyceride, total cholesterol, and apolipoprotein B levels and increasing HDL cholesterol levels in patients with primary hypercholesterolemia or mixed dyslipidemia. Fenofibric acid, the active ingredient of fenofibrate, was approved in 2008 as Trilipix, and similar indications were added for previously approved fenofibrate products. Fenofibric acid is the only fibrate approved for use with a statin for reducing triglyceride levels and raising HDL cholesterol levels in patients with mixed dyslipidemia and coronary heart disease or those who have equivalent risk levels and are receiving optimal statin therapy. This approval was based on three short-term studies examining the agent’s effects on lipid variables, but so far there are no data on direct clinical outcomes to support this indication. The Action to Control Cardiovascular Risk in Diabetes Fibrates in the Treatment of Dyslipidemias — Time for a Reassessment