Consistency of effect of ezetimibe/simvastatin compared with intensified lipid-lowering treatment strategies in obese and non-obese diabetic subjects

Jeffrey B Rosen, Jose G Jimenez, Valdis Pirags, Hella Vides, Rachid Massaad, Mary E Hanson, Philippe Brudi, Joseph Triscari, Jeffrey B Rosen, Jose G Jimenez, Valdis Pirags, Hella Vides, Rachid Massaad, Mary E Hanson, Philippe Brudi, Joseph Triscari

Abstract

Purpose: This post hoc analysis assessed switching to ezetimibe/simvastatin 10/20 mg vs doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg in subgroups of obese (BMI ≥30 kg/m2) and non-obese (BMI <30 kg/m2) diabetic subjects.

Methods: This was a randomized, double-blind, 12-week study of adults 18-79 years with cardiovascular disease with low-density lipoprotein cholesterol (LDL-C) ≥70 and ≤160 mg/dl. Percent change in LDL-C and other lipids was estimated.

Results: In obese subjects (n = 466), percent changes in LDL-C and most other lipids were greater with ezetimibe/simvastatin vs doubling the baseline statin dose or switching to rosuvastatin. In non-obese subjects (n = 342), percent changes in LDL-C, total cholesterol, non-HDL-C, Apo B and Apo A-I were greater with ezetimibe/simvastatin vs doubling the baseline statin dose or switching to rosuvastatin; and treatment with ezetimibe/simvastatin resulted in greater changes in triglycerides vs rosuvastatin and HDL-C vs doubling the baseline statin dose. The safety profiles were generally similar.

Conclusions: Regardless of baseline obesity status, switching to ezetimibe/simvastatin was more effective at reducing LDL-C, total cholesterol, non-HDL-C, and Apo B vs doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg.

Trial registration: ClinicalTrials.gov NCT00862251.

Figures

Figure 1
Figure 1
Flow of subjects through the study.
Figure 2
Figure 2
Least squares mean percent change from baseline in LDL-C in obese and non-obese subjects after 6 weeks of treatment. Bars represent standard error. (FAS population).
Figure 3
Figure 3
Percent of subjects achieving specified targets after 6 weeks of treatment (FAS population).
Figure 4
Figure 4
Least squares mean percent change from baseline in lipids, lipoproteins and hs-CRP after 6 weeks of treatment. Bars represent standard error. (FAS population). a. Obese subjects. b. non-obese subjects.
Figure 5
Figure 5
Least squares mean percent change from baseline in lipid ratios after 6 weeks of treatment. Bars represent standard error. (FAS population). a. obese subjects. b. non-obese subjects.

References

    1. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–234. doi: 10.1056/NEJM199807233390404.
    1. Simons LA, Simons J. Diabetes and coronary heart disease. N Engl J Med. 1998;339:1714–1715.
    1. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Expert Panel on the Identification, Evaluation, and Treatment of Overweight in Adults. Am J Clin Nutr. 1998;68:899–917.
    1. 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. doi: 10.1001/jama.285.19.2486.
    1. Genest J, McPherson R, Frohlich J, Anderson T, Campbell N, Carpentier A, Couture P, Dufour R, Fodor G, Francis GA, Grover S, Gupta M, Hegele RA, Lau DC, Leiter L, Lewis GF, Lonn E, Mancini GB, Ng D, Pearson GJ, Sniderman A, Stone JA, Ur E. Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult - 2009 recommendations. Can J Cardiol. 2009;2009(25):567–579.
    1. Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Eur J Cardiovasc Prev Rehabil. 2007;14:E1–E40. doi: 10.1097/01.hjr.0000277984.31558.c4.
    1. Hoenig MR, Kostner KM, Read SJ, Walker PJ, Atherton JJ. Implications of the obesity epidemic for statin therapy: shifting cholesterol metabolism to a high synthesis and low dietary absorption state. Endocr Metab Immune Disord Drug Targets. 2007;7:153–166. doi: 10.2174/187153007781662567.
    1. Howard BV, Ruotolo G, Robbins DC. Obesity and dyslipidemia. Endocrinol Metab Clin North Am. 2003;32:855–867. doi: 10.1016/S0889-8529(03)00073-2.
    1. Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH, Witztum JL. Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care. 2008;31:811–822. doi: 10.2337/dc08-9018.
    1. Bardini G, Giorda CB, Pontiroli AE, Le Grazie C, Rotella CM. Ezetimibe + simvastatin versus doubling the dose of simvastatin in high cardiovascular risk diabetics: a multicenter, randomized trial (the LEAD study) Cardiovasc Diabetol. 2010;9:20. doi: 10.1186/1475-2840-9-20.
    1. Goldberg RB, Guyton JR, Mazzone T, Weinstock RS, Polis A, Edwards P, Tomassini JE, Tershakovec AM. Ezetimibe/simvastatin vs atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia: the VYTAL study. Mayo Clin Proc. 2006;81:1579–1588. doi: 10.4065/81.12.1579.
    1. McCormack T, Harvey P, Gaunt R, Allgar V, Chipperfield R, Robinson P. Incremental cholesterol reduction with ezetimibe/simvastatin, atorvastatin and rosuvastatin in UK General Practice (IN-PRACTICE): randomised controlled trial of achievement of Joint British Societies (JBS-2) cholesterol targets. Int J Clin Pract. 2010;64:1052–1061. doi: 10.1111/j.1742-1241.2010.02429.x.
    1. Leiter LA, Betteridge DJ, Farnier M, Guyton JR, Lin J, Shah A, Johnson-Levonas AO, Brudi P. Lipid-altering efficacy and safety profile of combination therapy with ezetimibe/statin vs. statin monotherapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials. Diabetes Obes Metab. 2011;13:615–628. doi: 10.1111/j.1463-1326.2011.01383.x.
    1. Rosen JB, Jimenez JG, Pirags V, Vides H, Hanson ME, Massaad R, McPeters G, Brudi P, Triscari J. A comparison of efficacy and safety of an ezetimibe/simvastatin combination compared with other intensified lipid-lowering treatment strategies in diabetic patients with symptomatic cardiovascular disease. Cardiovasc Drugs Ther. 2012;10:277–286.
    1. Missault L, Averna M, Farnier M, Vaverkova H, Viikari J, Dong Q, Shah A, Johnson-Levonas A, Taggart W, Brudi P. Efficacy of Ezetimibe/Simvastatin 10/20 mg Versus Rosuvastatin 10 mg in High-Risk Patients With or Without Obesity. Combination Products in Therapy. 2011;1:1–15.
    1. Furman A, Meier JL, Malmstrom RA, Lopez JR, Schaefer S. Comparative efficacy of ezetimibe/simvastatin, rosuvastatin, and atorvastatin in uncontrolled hyperlipidemia patients. Am J Manag Care. 2011;17:538–544.
    1. Simonen PP, Gylling HK, Miettinen TA. Diabetes contributes to cholesterol metabolism regardless of obesity. Diabetes Care. 2002;25:1511–1515. doi: 10.2337/diacare.25.9.1511.
    1. Davidson MH, Maccubbin D, Stepanavage M, Strony J, Musliner T. Striated muscle safety of ezetimibe/simvastatin (Vytorin) Am J Cardiol. 2006;97:223–228. doi: 10.1016/j.amjcard.2005.08.038.
    1. US Food and Drug Administration. FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. Silver Springs, MD: US Department of Health & Human Services; 2013.

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