American Journal of Cardiology
Volume 102, Issue 11 , Pages 1495-1501 , 1 December 2008

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

  • Lawrence A. Leiter, MD

      Affiliations

    • St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada
    • Corresponding Author InformationCorresponding author: Tel: 416-867-7441; fax: 416-867-3696
    • ,
  • Harold Bays, MD

      Affiliations

    • Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky
    • ,
  • Scott Conard, MD

      Affiliations

    • University of Texas Southwestern Medical School, Dallas, Texas
    • ,
  • Steven Bird, MS

      Affiliations

    • Merck & Co., Inc., North Wales, Pennsylvania
    • ,
  • Joseph Rubino, MBA

      Affiliations

    • Merck & Co., Inc., North Wales, Pennsylvania
    • ,
  • Mary E. Hanson, PhD

      Affiliations

    • Merck & Co., Inc., North Wales, Pennsylvania
    • ,
  • Joanne E. Tomassini, PhD

      Affiliations

    • Merck & Co., Inc., North Wales, Pennsylvania
    • ,
  • Andrew M. Tershakovec, MD

      Affiliations

    • Merck & Co., Inc., North Wales, Pennsylvania

Received 9 September 2008 ,Revised 29 September 2008 ,Accepted 29 September 2008.

References 

  1. Pearson TA, Laurora I, Chu H, Kafonek S. The Lipid Treatment Assessment Project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med. 2000;160:459–467
  2. 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
  3. Davidson MH, Maki KC, Pearson TA, Pasternak RC, Deedwania PC, McKenney JM, et al. Results of the National Cholesterol Education (NCEP) Program Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II survey and implications for treatment under the recent NCEP Writing Group recommendations. Am J Cardiol. 2005;96:556–563
  4. Parke-Davis. Lipitor (atorvastatin calcium) tablets [package insert]. New York: Parke-Davis; 2007;
  5. Bristol-Myers Squibb. Pravachol (pravastatin sodium) tablets [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2007;
  6. Merck & Co. Inc.. Zocor (simvastatin) tablets [package insert]. Whitehouse Station, NJ: Merck & Co. Inc; 2007;
  7. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003;92:152–160
  8. AstraZeneca. Crestor (rosuvastatin calcium) tablets [package insert]. Wilmington, DE: AstraZeneca; 2007;
  9. Sudhop T, Lutjohann D, Kodal A, Igel M, Tribble DL, Shah S, et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation. 2002;106:1943–1948
  10. Dujovne CA, Ettinger MP, McNeer JF, Lipka LJ, LeBeaut AP, Suresh R, et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol. 2002;90:1092–1097
  11. Knopp RH, Gitter H, Truitt T, Bays H, Manion CV, Lipka LJ, et al. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J. 2003;24:729–741
  12. Lammert F, Wang DQ. New insights into the genetic regulation of intestinal cholesterol absorption. Gastroenterology. 2005;129:718–734
  13. Gagne C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol. 2002;90:1084–1091
  14. Davidson MH, McGarry T, Bettis R, Melani L, Lipka LJ, LeBeaut AP, et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol. 2002;40:2125–2134
  15. Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003;107:2409–2415
  16. Goldberg AC, Sapre A, Liu J, Capece R, Mitchel YB. Efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc. 2004;79:620–629
  17. Feldman T, Koren M, Insull W, McKenney J, Schrott H, Lewin A, et al. Treatment of high-risk patients with ezetimibe plus simvastatin co-administration versus simvastatin alone to attain National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. Am J Cardiol. 2004;93:1481–1486
  18. Pearson TA, Denke MA, McBride PE, Battisti WP, Brady WE, Palmisano J. A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the Ezetimibe Add-on to Statin for Effectiveness (EASE) trial. Mayo Clin Proc. 2005;80:587–595
  19. Masana L, Mata P, Gagne C, Sirah W, Cho M, Johnson-Levonas AO, et al. Long-term safety and tolerability profiles and lipid-modifying efficacy of ezetimibe coadministered with ongoing simvastatin treatment: a multicenter, randomized, double-blind, placebo-controlled, 48-week extension study. Clin Ther. 2005;27:174–184
  20. Davidson MH, Ballantyne CM, Kerzner B, Melani L, Sager PT, Lipka L, et al. Efficacy and safety of ezetimibe coadministered with statins: randomised, placebo-controlled, blinded experience in 2382 patients with primary hypercholesterolemia. Int J Clin Pract. 2004;58:746–755
  21. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the 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). JAMA. 2001;285:2486–2497
  22. 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
  23. Liang KY, Zeger SL. Longitudinal data analysis of continuous and discrete responses for pre-post designs. Sankya Series B. 2000;62:134–148
  24. Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985;4:213–226
  25. Stein E, Stender S, Mata P, Sager P, Ponsonnet D, Melani L, et al. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Am Heart J. 2004;148:447–455
  26. Merck/Schering-Plough Pharmaceuticals. Zetia (ezetimibe) [package insert]. North Wales, PA: Merck/Schering-Plough Pharmaceuticals; 2008;
  27. Melani L, Mills R, Hassman D, Lipetz R, Lipka L, LeBeaut A, et al. Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Eur Heart J. 2003;24:717–728
  28. Bissonnette S, Habib R, Sampalis F, Boukas S, Sampalis JS. Efficacy and tolerability of ezetimibe 10 mg/day coadministered with statins in patients with primary hypercholesterolemia who do not achieve target LDL-C while on statin monotherapy: A Canadian, multicentre, prospective study—the Ezetrol Add-On Study. Can J Cardiol. 2006;22:1035–1044

 This work was supported by Merck/Schering-Plough Pharmaceuticals, North Wales, Pennsylvania.

PII: S0002-9149(08)01670-6

doi: 10.1016/j.amjcard.2008.09.076

American Journal of Cardiology
Volume 102, Issue 11 , Pages 1495-1501 , 1 December 2008

Article Tools

* Image Usage & Resolution