Optimal lipid modification: the rationale for combination therapy

Background: An emphasis on more aggressive lipid-lowering, particularly of low-density lipoprotein cholesterol, to improve patient outcomes has led to an increased use of combination lipid-lowering drugs. This strategy, while potentially beneficial, has triggered concerns regarding fears of adverse effects, harmful drug interactions, and patient nonadherence. Objective: To present key data regarding combination lipid-altering therapy including use, rationale, major trials, benefits, potential adverse effects, compliance issues, and limitations. Method: Literature was obtained from MEDLINE (1966 June 2005) and references from selected articles. Results: A substantial body of evidence from epidemiological data and clinical trials indicates that aggressive lipid modification, especially low-density lipoprotein reduction, is associated with reduced cardiovascular events. Numerous studies utilizing various combinations of cholesterol-lowering agents including statin/fibrate, statin/niacin, statin/bile acid resin, and statin/ezetimibe have demonstrated significant changes in the lipid profile with acceptable safety. Long-term trials of combination therapy evaluating clinical outcomes or surrogate markers of cardiovascular disease, while limited, are promising. Conclusion: Combining lipid-altering agents results in additional improvements in lipoproteins and has the potential to further reduce cardiovascular events beyond that of monotherapy.