Management of mixed dyslipidemia in patients with or at risk for cardiovascular disease: A role for combination fibrate therapy

Background: Lowering low-density lipoprotein cholesterol (LDL-C) is the primary focus of the management of dyslipidemia in patients with or at risk for cardiovascular disease. However, use of a statin alone may be insufficient for the treatment of mixed dyslipidemia, which is characterized by low levels of high-density lipoprotein cholesterol and elevated levels of triglycerides, with or without elevated levels of LDL-C. Objective: This report reviews the evidence for the efficacy and tolerability of different combination treatments for the management of mixed dyslipidemia, as supported by clinical-trial data and recommended by national guidelines. Methods: Using the terms lipid-modifying therapy, combination therapy, combination statin-fibrate therapy, and mixed dyslipidemia, a search of PubMed was conducted (completed in April 2007, updated to October 2007) to identify English-language publications and pertinent studies of fibrate combination therapy in patients with mixed dyslipidemia, including those with diabetes or the metabolic syndrome. Results: National guidelines recommend the addition of either niacin (nicotinic acid) or a fibrate to statin therapy in patients with mixed dyslipidemia to achieve better overall lipid control. Fibrates do not have detrimental effects on uric acid levels or glycemic control in patients with diabetes or the metabolic syndrome. Based on data from the US Food and Drug Administration Adverse Event Reporting System indicating that gemfibrozil plus a statin was associated with a 15-fold higher risk of rhabdomyolysis than fenofibrate plus a statin, fenofibrate may be the fi-brate of choice for use in combination with a statin. As reported by the Fenofibrate Intervention and Event Lowering in Diabetes study, fenofibrate treatment has also been associated with microvascular benefits in patients with type 2 diabetes, which is consistent with preliminary evidence from the Diabetes Atherosclerosis Intervention Study. Conclusion: The addition of fenofibrate to statin therapy may be a useful strategy for the management of mixed dyslipidemia in patients with or at risk for cardiovascular disease.