Lipid-Altering Efficacy and Safety of Ezetimibe/Simvastatin Versus Atorvastatin in Patients With Hypercholesterolemia and the Metabolic Syndrome (from the VYMET Study)

Received 31 March 2009; received in revised form 7 May 2009; accepted 7 May 2009.

Patients with the metabolic syndrome are at an increased risk of cardiovascular disease and might require intensive lipid therapy. Many patients remain at the starting dose of lipid therapy and might not be titrated up to a higher dose. The present double-blind, randomized, 6-week study assessed the lipid-lowering efficacy of ezetimibe/simvastatin 10/20 mg versus atorvastatin 10 or 20 mg, and ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in 1,128 patients with hypercholesterolemia and the metabolic syndrome. The primary end point was the percentage of change from baseline in low-density lipoprotein (LDL) cholesterol. Additional end points included changes in other lipids, lipoprotein ratios, high-sensitivity C-reactive protein, and attainment of prespecified lipid levels. Significantly greater improvements in the levels of LDL cholesterol, non–high-density lipoprotein cholesterol, apolipoprotein B, and lipid/lipoprotein ratios resulted with ezetimibe/simvastatin compared with atorvastatin at all specified dose comparisons (p <0.001). The attainment of prespecified LDL cholesterol and non–high-density lipoprotein cholesterol levels was also significantly greater with ezetimibe/simvastatin than with atorvastatin at all dose comparisons (p <0.05). High-density lipoprotein cholesterol increases were significantly greater with ezetimibe/simvastatin 10/20 mg than with atorvastatin 10 mg (p <0.05) and ezetimibe/simvastatin 10/40 mg than with atorvastatin 40 mg (p <0.01). The changes in triglycerides, very low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein were similar for both treatments. The incidence of liver, muscle, and gastrointestinal-, hepatitis- and allergic reaction/rash-related adverse events were low and generally similar to those in previous studies of ezetimibe/simvastatin and/or atorvastatin. In conclusion, ezetimibe/simvastatin was more likely to result in lipid treatment end points than atorvastatin and was generally well tolerated at the doses compared in our patients.

a University of Iowa College of Public Health, Iowa City, Iowa

b Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, Texas

c University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

d Methodist Hospital Research Institute, Houston, Texas

e Department of Medical Endocrinology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark

f Clinical Research of South Florida, Coral Gables, Florida

g Merck & Company, Incorporated, North Wales, Pennsylvania

Corresponding author: Tel: (319) 384-5040; fax: (319) 384-5004

This study was funded by Merck/Schering-Plough Pharmaceuticals, North Wales, Pennsylvania; the study sponsor, Merck & Company, Incorporated, Whitehouse Station, New Jersey, facilitated the design and conduct of the study and the collection and analysis of the study data.

Dr. Robinson received research support from AstraZeneca, Abbott, Aegerion, Bristol-Meyers Squibb, Hoffman LaRoche, Merck, and Merck/Schering-Plough Pharmaceuticals; honoraria from Merck/Schering-Plough Pharmaceuticals; and has served as a consultant and/or member of an advisory board for Merck/Schering-Plough Pharmaceuticals. Dr. Ballantyne received research support from Abbott, AstraZeneca, GSK, Merck, Pfizer, Sanofi-Synthelabo, Schering-Plough, and Takeda; has served on the Speakers' Bureau of AstraZeneca, GSK, Merck, Merck/Schering-Plough Pharmaceuticals, Pfizer, Reliant, and Schering-Plough; has received honoraria from AstraZeneca, Merck, Abbott, Atherogenics, GSK, Merck/Schering-Plough Pharmaceuticals, Novartis, Pfizer, Sanofi-Synthelabo, Schering-Plough, and Takeda; and has served as a consultant or advisory board member for Abbott, AstraZeneca, Atherogenics, GSK, Merck, Merck/Schering-Plough Pharmaceuticals, Novartis, Pfizer, Sanofi-Synthelabo, Schering-Plough, and Takeda. Dr. Grundy received honoraria from Merck/Schering-Plough Pharmaceuticals and served as a consultant and/or advisory board member for Merck, Merck/Schering-Plough Pharmaceuticals, AstraZeneca, Pfizer, and GSK. Dr. Hsueh received honoraria from Merck/Schering-Plough Pharmaceuticals and served on the Speakers' Bureau of Merck/Schering-Plough Pharmaceuticals and GSK; and served as a consultant or member of the advisory board for Novartis and Daiicho Sankyo. Dr. Parving received honoraria from Merck/Schering-Plough Pharmaceuticals. Dr. Rosen received research support from Roche, GSK, and Sankyo; and has received honoraria from Merck/Schering-Plough Pharmaceuticals. Drs. Adewale, Tershakovec, and Tomassini and Mr. Polis are employees of Merck & Company, Incorporated, and own stock and/or stock options in the company.

PII: S0002-9149(09)01026-1

doi:10.1016/j.amjcard.2009.05.003

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