Fibrates: What Have We Learned in the Past 40 Years?

James M. Backes, Pharm.D.; Cheryl A. Gibson, Ph.D.; Janelle F. Ruisinger, Pharm.D.; Patrick M. Moriarty, M.D.

Disclosures

Pharmacotherapy. 2007;27(3):412-424. 

In This Article

Abstract and Introduction

Abstract

The prominent use of fibric acid derivatives has lessened over the years because of unimpressive results in major clinical trials, safety concerns, and the emergence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Clofibrate was widely used in the 1970s, but after publication of results from two major trials demonstrating only modest reductions in the rate of coronary heart disease (CHD) and concerns regarding an increase in the frequency of gallstones and overall mortality, its use subsided dramatically. With the introduction of gemfibrozil in the 1980s came a renewed interest in the class, which was also supported by the published results of the Helsinki Heart Study; however, despite a significant reduction in CHD events and a sound safety profile, overall mortality was comparable to that with placebo. Again, in the 1990s, awareness of the fibrates was heightened with the availability of fenofibrate and the findings of another major trial using gemfibrozil, the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT), which demonstrated impressive results in reducing cardiovascular events. To further strengthen the VA-HIT results, numerous post hoc analyses were performed on the data of major trials of fibrate therapy among patients with mixed dyslipidemia, with similar findings. Recently, however, data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were published, indicating mixed results. Nearly 40 years after the introduction of the fibrates, practitioners are still contemplating the role of these agents in the treatment of CHD.

Introduction

At one time, fibric acid derivatives were the mainstay for the treatment of hypercholes-terolemia. Mediocre results coupled with safety concerns from early studies and the introduction of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have caused fibrates to take a backseat to newer therapies. However, more recent trials and post hoc analyses of studies of fibrates look promising. In addition, the focus over the past 15 years has been on low-density lipoprotein cholesterol (LDL) reduction with statin therapy. During this time, results have been published for more than 30 major trials with statins that enrolled over 100,000 patients compared with only eight trials with fibrates that involved approximately 18,500 patients.[1,2]

Fibrates were first introduced in the United States with the approval of clofibrate in 1967, which was followed by gemfibrozil in the early 1980s, and fenofibrate in 1998 (fenofibrate had been used in Europe since the 1970s). Although clofibrate is still available, its use is very limited. The widely prescribed fibrates in the United States include gemfibrozil and fenofibrate, whereas bezafibrate and ciprofibrate are available in other countries.

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