A review of lipid-modifying drugs used alone and in combination

PURPOSE: To review the pharmacologic properties of the 5 major classes of lipid-modifying agents and summarize the findings from major clinical studies assessing the efficacy and safety of single lipid-modifying agents and combination pharmacotherapy for lipid disorders. EPIDEMIOLOGY: Coronary heart disease (CHD) affects 13 million Americans and is the cause of 1 in every 5 deaths in the United States. Almost 50% of the adult population has a low-density lipoprotein cholesterol (LDL-C) level ≥ 30 mg/dL (considered borderline-high to high). It has been estimated that a population-wide decrease in total cholesterol levels of 10% would reduce the incidence of CHD by 30%. REVIEW SUMMARY: Of the 5 classes of lipid-modifying agents (statins, bile acid sequestrants [BAS], fibrates, niacin, and cholesterol absorption inhibitors [ezetimibe]), all but ezetimibe have been shown to reduce the risk of cardiovascular events during long-term treatment. Statins are the most potent at reducing LDL-C levels, whereas fibrates are most potent at reducing triglyceride levels, and niacin is most potent at increasing levels of high-density lipoprotein cholesterol. Eight of the 10 possible combinations of classes have been studied in clinical trials. Combination therapy provides additional favorable changes in lipid levels compared with monotherapy, and combinations with complementary mechanisms are particularly useful in patients with mixed hyperlipidemia. Caution should be exercised when combining a statin with a fibrate because of the increased risk of myopathy. Hepatic enzyme levels should be monitored when statins are combined with niacin or ezetimibe. The combination of a statin plus a BAS does not increase the incidence of adverse events relative to either agent given alone. TYPE OF AVAILABLE EVIDENCE: Randomized controlled trials, nationally recognized guidelines, systematic reviews/meta-analyses. GRADE OF AVAILABLE EVIDENCE: Good. CONCLUSION: As the latest guidelines from the National Cholesterol Education Program Adult Treatment Panel III mandate more aggressive treatment of lipid disorders linked to CHD, it is likely that use of combination therapy for lipid disorders will increase. A number of possible combinations are available, all providing incremental lipid-lowering efficacy compared with monotherapy. However, physicians should carefully assess patient needs, potential adverse events, and drug interactions when choosing the right combination for an individual patient.