Cardiology Express Report

Publication date: 2006-03-31

The Benefits of Fibrate Therapy for Reducing Cardiovascular Risk in Patients with Diabetes

This report was reviewed for medical and scientific accuracy by John B. Kostis, MD, FACC, FACP, John G. Detwiler Professor of Cardiology; Professor of Medicine and Pharmacology; Chairman, Department of Medicine; University of Medicine & Dentistry of New Jersey—Robert Wood Johnson Medical School; New Brunswick, New Jersey

Expert Commentary

Sergio Fazio, MD, PhD, Professor of Medicine and Pathology; Co-Director, Atherosclerosis Research Unit; Director, Clinical Nutrition Research Center, Vanderbilt University Medical Center, Nashville, Tennessee

According to the results of a recently published study in The Lancet, long-term fenofibrate therapy reduces the risk of cardiovascular events, primarily nonfatal myocardial infarctions and revascularizations among patients with type 2 diabetes, and is particularly effective in subjects without prior coronary heart disease (CHD).¹ The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a 5-year, multinational, double-blind, randomized, placebo-controlled trial that evaluated the effects of fenofibrate therapy on CHD morbidity and mortality in 9,795 patients with type 2 diabetes. This landmark study represents the largest clinical outcomes study ever conducted with a lipid-modifying medication in patients with type 2 diabetes.

After adjustment for the 2-fold higher use of statin therapy in the placebo versus the fenofibrate treatment arm, fenofibrate therapy was associated with a 19% reduction in the primary end point of cardiovascular events (cardiovascular death and nonfatal myocardial infarctions; P = .01) and a 24% reduction in nonfatal myocardial infarction (P<.010). Furthermore, fenofibrate treatment was associated with a 21% reduction in coronary revascularization (P = .003). Interestingly, indices of microvascular function also were improved by treatment. Compared with placebo, the rate of progression to albuminuria was significantly lower for patients treated with fenofibrate (P<.002) and fewer patients required laser treatments for retinopathy (P = .0003). In addition, fenofibrate was generally well-tolerated and had a good safety profile irrespective of concomitant therapy, including the almost 1,000 patients taking a combination of fenofibrate and statin. Therefore, these results demonstrate that fenofibrate can provide beneficial effects on both macrovascular and microvascular complications in patients with diabetes.

Cardiovascular disease is a leading cause of morbidity and mortality among patients with diabetes. Indeed, cardiovascular disease accounts for 65% of all deaths in persons with diabetes.² Most diabetic patients with cardiovascular complications have abnormal lipid profiles, and lipid-lowering agents are recommended to reduce the risk of cardiovascular disease.^3-5 Decreasing low-density lipoprotein (LDL)-cholesterol remains the first priority in the management of diabetic dyslipidemia, and statin therapy is widely used to achieve this goal. However, patients with diabetes commonly have high triglycerides, low high-density lipoprotein (HDL)-cholesterol, and a preponderance of small dense LDL particles, a lipid profile not amenable to full adjustment through statin therapy.

It is well established that patients with type 2 diabetes have LDL-cholesterol levels similar to those of individuals without diabetes,³ but often present with atherogenic dyslipidemia (high triglycerides, low HDL-cholesterol).^3,6 In diabetic patients with cardiovascular disease, this pattern is significantly predictive of the incidence of vascular events.6 Therefore, improving HDL-cholesterol and triglyceride levels should be considered an integral aspect of lipid management in patients with diabetes.^4,6

Fibric acid derivatives, or fibrates, effectively lower triglycerides and increase HDL-cholesterol, and therefore are a logical intervention for diabetic dyslipidemia.⁷ In addition, fibrates might als