Optimal lipid modification: the rationale for combination therapy

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Authors: James M Backes, Cheryl A Gibson, Patricia A Howard

Published Date January 2005 Volume 2005:1(4) Pages 317 - 331

DOI: http://dx.doi.org/10.2147/VHRM.S

James M Backes¹, Cheryl A Gibson², Patricia A Howard³

¹Department of Pharmacy Practice, Lipid, Atherosclerosis, Metabolic and LDL Apheresis Center, University of Kansas Medical Center, Kansas City, KS, USA; ²Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA; ³Department of Pharmacy Practice, University of Kansas School of Pharmacy, Kansas City, KS, USA

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.

Keywords: combination therapy, coronary heart disease, hypercholesterolemia, lipid-lowering, low-density lipoprotein, statins