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DYSLIPIDEMIA

The Impact of Ezetimibe on Endothelial Function and Other Markers of Cardiovascular Risk

Clinical Research and Drug Development Fellow, Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill

Alan L Hinderliter, MD

Associate Professor of Medicine, Division of Cardiology, School of Medicine, University of North Carolina at Chapel Hill

Craig R Lee, PharmD PhD

Assistant Professor of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill

Reprints: Dr. Lee, UNC Eshelman School of Pharmacy, 2317 Kerr Hall, CB 7569, Chapel Hill, NC 27599, fax 919/962-0644, craig_lee{at}unc.edu

OBJECTIVE: To review the published literature characterizing the impact of ezetimibe-containing lipid-lowering regimens on endothelial function and other markers of cardiovascular risk and discuss the potential relevance of these effects to the clinical benefit of ezetimibe.

DATA SOURCES: A MEDLINE search (2000–August 2009) was completed using the key words ezetimibe, statins, endothelial function, flow-mediated dilation, pleiotropic, and inflammation to identify relevant literature. Bibliographies of identified literature were reviewed for additional references.

STUDY SELECTION AND DATA EXTRACTION: All clinical studies published in English that evaluated the effect of ezetimibe on ancillary endpoints of cardiovascular disease risk, including endothelial function, inflammation, thrombosis, and oxidative stress, were evaluated.

DATA SYNTHESIS: Recent studies in patients with coronary artery disease (CAD), heart failure, and hypercholesterolemia have demonstrated that treatment with ezetimibe for 4–12 weeks elicits no improvement of endothelial function or other measures of cardiovascular disease risk. In contrast, other studies have reported that ezetimibe improves endothelial function in certain patient populations, including those with rheumatoid arthritis, CAD with type 2 diabetes, and metabolic syndrome. However, the statin monotherapy comparator groups in these studies that yielded equivalent reductions in cholesterol were superior, or at least equivalent to, ezetimibe-containing regimens in the improvement of these ancillary endpoints.

CONCLUSIONS: Overall, the evidence to date suggests that administration of ezetimibe, either as monotherapy or in combination with a statin, exerts minimal beneficial effects on endothelial function and other ancillary measures of cardiovascular disease risk beyond those conferred by its cholesterol-lowering effects. Studies with larger sample sizes and follow-up beyond 12 weeks remain necessary to further define the impact of ezetimibe on the processes integral to the pathogenesis and progression of cardiovascular disease.

Key Words: endothelial function, ezetimibe, flow-mediated dilation, inflammation, pleiotropic, statins

Published Online, November 17, 2009. www.theannals.com, DOI 10.1345/aph.1M302