American Journal of Cardiology
Volume 103, Issue 12 , Pages 1694-1702 , 15 June 2009

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

  • Jennifer G. Robinson, MD, MPH

      Affiliations

    • University of Iowa College of Public Health, Iowa City, Iowa
    • Corresponding Author InformationCorresponding author: Tel: (319) 384-5040; fax: (319) 384-5004
    • ,
  • Christie M. Ballantyne, MD

      Affiliations

    • Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, Texas
    • ,
  • Scott M. Grundy, MD, PhD

      Affiliations

    • University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
    • ,
  • Willa A. Hsueh, MD

      Affiliations

    • Methodist Hospital Research Institute, Houston, Texas
    • ,
  • Hans-Henrik Parving, MD

      Affiliations

    • Department of Medical Endocrinology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark
    • ,
  • Jeffrey B. Rosen, MD

      Affiliations

    • Clinical Research of South Florida, Coral Gables, Florida
    • ,
  • Adeniyi J. Adewale, PhD

      Affiliations

    • Merck & Company, Incorporated, North Wales, Pennsylvania
    • ,
  • Adam B. Polis, MA

      Affiliations

    • Merck & Company, Incorporated, North Wales, Pennsylvania
    • ,
  • Joanne E. Tomassini, PhD

      Affiliations

    • Merck & Company, Incorporated, North Wales, Pennsylvania
    • ,
  • Andrew M. Tershakovec, MD, MPH

      Affiliations

    • Merck & Company, Incorporated, North Wales, Pennsylvania

Received 31 March 2009 ,Revised 7 May 2009 ,Accepted 7 May 2009.

References 

  1. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation. 2005;112:2735–2752
  2. Grundy SM. Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol. 2006;47:1093–1100
  3. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–3421
  4. Grundy SM, Cleeman JI, Merz CN, Brewer HB, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. J Am Coll Cardiol. 2004;44:720–732
  5. Smith SC, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. Circulation. 2006;113:2363–2372
  6. Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH, et al. Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology foundation. Diab Care. 2008;31:811–822
  7. Abate N, Catapano AL, Ballantyne CM, Davidson M, Polis A, Smugar S, et al. Effect of ezetimibe/simvastatin versus atorvastatin or rosuvastatin on modifying lipid profiles in patients with diabetes, metabolic syndrome, or neither: results of two subgroup analyses. J Clin Lipidol. 2008;2:91–105
  8. Deedwania PC, Hunninghake DB, Bays HE, Jones PH, Cain VA, Blasetto JW. Effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on atherogenic dyslipidemia in patients with characteristics of the metabolic syndrome. Am J Cardiol. 2005;95:360–366
  9. Denke M, Pearson T, McBride P, Gazzara RA, Brady WE, Tomassini JE, et al. Ezetimibe added to ongoing statin therapy improves LDL-C goal attainment and lipid profile in patients with diabetes or metabolic syndrome. Diab Vasc Dis Res. 2006;3:93–102
  10. Feldman T, Ose L, Shah A, Zakson M, Meehan A, Johnson-Levonas A, et al. Efficacy and safety of ezetimibe/simvastatin versus simvastatin monotherapy in hypercholesterolemic patients with metabolic syndrome. Metab Syndr Relat Disord. 2007;5:13–21
  11. Simons L, Tonkon M, Masana L, Maccubbin D, Shah A, Lee M, et al. Effects of ezetimibe added to on-going statin therapy on the lipid profile of hypercholesterolemic patients with diabetes mellitus or metabolic syndrome. Curr Med Res Opin. 2004;20:1437–1445
  12. Stalenhoef AFH, Ballantyne CM, Sarti C, Murin J, Tonstad S, Rose H, et al. A comparative study with rosuvastatin in subjects with metabolic syndrome: results of the COMETS study. Eur Heart J. 2005;26:2664–2672
  13. Steiner G. Lipid lowering in the patients with prediabetes/metabolic syndrome: what is the evidence?. Curr Opin Lipidol. 2008;19:585–591
  14. Deedwania P, Barter P, Carmena R, Fruchart JC, Grundy SM, Haffner S, et al. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the treating to new targets study. Lancet. 2006;368:919–928
  15. Stender S, Schuster H, Barter P, Watkins C, Kallend D. Comparison of rosuvastatin with atorvastatin, simvastatin and pravastatin in achieving cholesterol goals and improving plasma lipids in hypercholesterolaemic patients with or without the metabolic syndrome in the MERCURY I trial. Diab Obes Metab. 2005;7:430–438
  16. Vytorin (ezetimibe/simvastatin) [package insert]. North Wales, PA: Merck/Schering-Plough Pharmaceuticals; 2009;
  17. Lipitor (atorvastatin calcium) tablets [package insert]. New York: Parke-Davis; 2009;
  18. Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985;4:213–226
  19. Genest J, Frohlich J, Fodor G, McPherson R. Recommendations for the management of dyslipidemia and the prevention of cardiovascular disease: summary of the 2003 update. Can Med Assoc J. 2003;69:921–924
  20. Kastelein JJP, van der Steeg WA, Holme I, Gaffney M, Cater NB, Barter P, et al. Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment. Circulation. 2008;117:3002–3009
  21. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;107:499–511
  22. Ballantyne CM, Abate N, Yuan Z, King TR, Palmisano J. Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: the Vytorin Versus Atorvastatin (VYVA) study. Am Heart J. 2005;149:463–474
  23. Conard SE, Bays HE, Leiter LA, Bird SR, Rubino J, Lowe RS, et al. Efficacy and safety of ezetimibe added on to atorvastatin (20 mg) versus uptitration of atorvastatin (to 40 mg) in hypercholesterolemic patients at moderately high risk for coronary heart disease. Am J Cardiol. 2008;102:1489–1494
  24. Goldberg RB, Guyton JR, Mazzone T, Weinstock RS, Polis A, Edwards P, et al. Ezetimibe/simvastatin vs atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia: the VYTAL study. Mayo Clin Proc. 2006;81:1579–1588
  25. Leiter LA, Bays H, Conard S, Bird S, Rubino J, Hanson ME, et al. Efficacy and safety of ezetimibe added on to atorvastatin (40 mg) compared with uptitration of atorvastatin (to 80 mg) in hypercholesterolemic patients at high risk of coronary heart disease. Am J Cardiol. 2008;102:1495–1501
  26. Westerbacka J, Corner A, Tiikkainen M, Tamminen M, Vehkavaara S, Hakkinen AM, et al. Women and men have similar amounts of liver and intra-abdominal fat, despite more subcutaneous fat in women: implications for sex differences in markers of cardiovascular risk. Diabetologia. 2004;47:1360–1369
  27. Schindhelm RK, Diamant M, Dekker JM, Tushuizen ME, Teerlink T, Heine RJ. Alanine aminotransferase as a marker of non-alcoholic fatty liver disease in relation to type 2 diabetes mellitus and cardiovascular disease. Diab Metab Res Rev. 2006;22:437–443

 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

American Journal of Cardiology
Volume 103, Issue 12 , Pages 1694-1702 , 15 June 2009

Article Tools

* Image Usage & Resolution