Lipid-altering efficacy of ezetimibe/simvastatin 10/40 mg compared with doubling the statin dose in patients admitted to the hospital for a recent coronary event: the INFORCE study
2008; Wiley; Volume: 62; Issue: 4 Linguagem: Inglês
10.1111/j.1742-1241.2008.01697.x
ISSN1742-1241
AutoresJohn Reckless, Peter J. Henry, T. Pomykaj, Sanghyun Lim, Rachid Massaad, K. Vandormael, Amy O. Johnson‐Levonas, Kinga Lis, Philippe Brudi, Christopher Allen,
Tópico(s)Health Systems, Economic Evaluations, Quality of Life
ResumoInternational Journal of Clinical PracticeVolume 62, Issue 4 p. 539-554 Lipid-altering efficacy of ezetimibe/simvastatin 10/40 mg compared with doubling the statin dose in patients admitted to the hospital for a recent coronary event: the INFORCE study J. P. D. Reckless, J. P. D. Reckless Royal United Hospital, Bath, UKSearch for more papers by this authorP. Henry, P. Henry Hospital Lariboisiere, Paris, FranceSearch for more papers by this authorT. Pomykaj, T. Pomykaj Städtisches Klinikum, Braunschweig, GermanySearch for more papers by this authorS. T. Lim, S. T. Lim National Heart Center, SingaporeSearch for more papers by this authorR. Massaad, R. Massaad Merck Sharp & Dohme, Brussels, BelgiumSearch for more papers by this authorK. Vandormael, K. Vandormael Merck Sharp & Dohme, Brussels, BelgiumSearch for more papers by this authorA. O. Johnson-Levonas, A. O. Johnson-Levonas Merck Research Laboratories, Rahway, NJ, USASearch for more papers by this authorK. Lis, K. Lis Merck Research Laboratories, Rahway, NJ, USASearch for more papers by this authorP. Brudi, P. Brudi Merck Schering-Plough, Whitehouse Station, NJ, USASearch for more papers by this authorC. Allen, C. Allen Merck Research Laboratories, Rahway, NJ, USASearch for more papers by this author J. P. D. Reckless, J. P. D. Reckless Royal United Hospital, Bath, UKSearch for more papers by this authorP. Henry, P. Henry Hospital Lariboisiere, Paris, FranceSearch for more papers by this authorT. Pomykaj, T. Pomykaj Städtisches Klinikum, Braunschweig, GermanySearch for more papers by this authorS. T. Lim, S. T. Lim National Heart Center, SingaporeSearch for more papers by this authorR. Massaad, R. Massaad Merck Sharp & Dohme, Brussels, BelgiumSearch for more papers by this authorK. Vandormael, K. Vandormael Merck Sharp & Dohme, Brussels, BelgiumSearch for more papers by this authorA. O. Johnson-Levonas, A. O. Johnson-Levonas Merck Research Laboratories, Rahway, NJ, USASearch for more papers by this authorK. Lis, K. Lis Merck Research Laboratories, Rahway, NJ, USASearch for more papers by this authorP. Brudi, P. Brudi Merck Schering-Plough, Whitehouse Station, NJ, USASearch for more papers by this authorC. Allen, C. Allen Merck Research Laboratories, Rahway, NJ, USASearch for more papers by this author First published: 06 March 2008 https://doi.org/10.1111/j.1742-1241.2008.01697.xCitations: 25 J. P. D. Reckless,Royal United Hospital, Bath, UKTel.: + 44 (0) 1225 824527Fax: + 44 (0) 1225 824529 Emails: [email protected], [email protected] Disclosure Several of the named authors are Merck or Schering-Plough employees, and as such, may hold stock in the company. Other authors were involved in the conduct of a study that was funded by Merck/Schering-Plough Pharmaceuticals, North Wales, Pennsylvania. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Summary Background: The aim of this study was to investigate the efficacy and safety profile of switching to ezetimibe/simvastatin (Eze/Simva) 10/40 mg compared with doubling the statin dose upon discharge in patients taking a statin and admitted to the hospital for the investigation of a coronary event. Design: This phase IV, multi-centre, randomised, open-label, active-controlled, parallel group study enrolled 424 patients (aged ≥ 18 years) hospitalised for an acute coronary event and taking a stable dose of a statin (≥ 6 weeks) that could be doubled per the product label. Upon discharge from the hospital, patients were stratified by their statin dose/potency (high, medium and low) and randomised 1 : 1 to doubling of the statin dose (n = 211) or Eze/Simva 10/40 mg (n = 213) for 12 weeks. The primary efficacy variable was the absolute low-density lipoprotein cholesterol (LDL-C) value (mmol/l) at study end-point. Results: Mean baseline LDL-C for the two treatment groups were 2.48 and 2.31 mmol/l for the Eze/Simva and statin groups respectively. At study end-point, least squares mean LDL-C values were 1.74 mmol/l in the Eze/Simva group and 2.22 mmol/l in the statin group resulting in a significant between-group difference of −0.49 mmol/l (p ≤ 0.001). Eze/Simva 10/40 mg also produced significantly lower total cholesterol (−0.49 mmol/l), non-high-density lipoprotein cholesterol [(non-HDL-C); −0.53 mmol/l] and apolipoprotein B (−0.14 mmol/l) values compared with doubling the statin dose (p ≤ 0.001 for all). Both treatments produced similar effects on triglycerides, C-reactive protein and HDL-C; the between treatment group differences were not significant (p ≥ 0.160). Significantly more patients achieved LDL-C levels < 2.5 (< 100 mg/dl; 86% vs. 72%), < 2.0 (< 77 mg/dl; 70% vs. 42%) and < 1.8 mmol/l (< 70 mg/dl; 60% vs. 31%) with Eze/Simva than statin (all p ≤ 0.001). Eze/Simva was generally well tolerated, with a safety profile similar to statin. There were no differences in the incidences of liver transaminases ≥ 3 × upper limit of normal (ULN) or creatine kinase ≥ 10 × ULN between the groups. Conclusions: In patients taking a statin and admitted to the hospital for investigation of a coronary event, treatment with Eze/Simva 10/40 mg for 12 weeks produced greater improvements in lipids with a similar safety profile compared with doubling of the statin dose. References 1 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– 97. 2 JBS 2: Joint British Societies’ guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005; 91 (Suppl. 5): v1– 52. 3 Downs JR, Clearfield M, Weis S et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279: 1615– 22. 4 Sacks FM, Pfeffer MA, Moye LA et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 1001– 9. 5 Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 1998; 97: 1440– 5. 6 Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998; 339: 1349– 57. 7 Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993; 269: 3015– 23. 8 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7– 22. 9 LaRosa JC, Grundy SM, Waters DD et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352: 1425– 35. 10 Pedersen TR, Faergeman O, Kastelein JJ et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005; 294: 2437– 45. 11 Cannon CP, Braunwald E, McCabe CH et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350: 1495– 504. 12 Ray KK, Cannon CP, McCabe CH et al. Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial. J Am Coll Cardiol 2005; 46: 1405– 10. 13 De Lemos JA, Blazing MA, Wiviott SD et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004; 292: 1307– 16. 14 Schwartz GG, Olsson AG, Ezekowitz MD et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001; 285: 1711– 8. 15 Hulten E, Jackson JL, Douglas K, George S, Villines TC. The effect of early, intensive statin therapy on acute coronary syndrome: a meta-analysis of randomized controlled trials. Arch Intern Med 2006; 166: 1814– 21. 16 Fintel D, Joyce A, Mackell J, Graff J, Kuntze E, Ollendorf DA. Reduced mortality rates after intensive statin therapy in managed-care patients. Value Health 2007; 10: 161– 9. 17 Afilalo J, Majdan AA, Eisenberg MJ. Intensive statin therapy in acute coronary syndromes and stable coronary heart disease: a comparative meta-analysis of randomised controlled trials. Heart 2007; 93: 914– 21. 18 Grundy SM, Cleeman JI, Merz CN et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110: 227– 39. 19 Smith SC Jr, Allen J, Blair SN 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– 72. 20 Graham I, Atar D, Borch-Johnsen K et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts). Eur Heart J 2007; 28: 2375– 414. 21 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– 67. 22 Vanuzzo D, Pilotto L, Ambrosio GB et al. Potential for cholesterol lowering in secondary prevention of coronary heart disease in Europe: findings from EUROASPIRE study. Atherosclerosis 2000; 153: 505– 17. 23 Davidson MH, Maki KC, Pearson TA 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– 63. 24 Laforest L, Souchet T, Ritleng C et al. LDL-cholesterol goal attainment according to cardiovascular risk level in patients receiving lipid lowering therapy in primary care. Eur Heart J 2007; 28: 497. 25 Miller M. Optimal treatment of dyslipidemia in high-risk patients: intensive statin treatment or combination therapy? Prev Cardiol 2007; 10: 31– 5. 26 Andrews TC, Ballantyne CM, Hsia JA, Kramer JH. Achieving and maintaining National Cholesterol Education Program low-density lipoprotein cholesterol goals with five statins. Am J Med 2001; 111: 185– 91. 27 Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 2004; 109 (23 Suppl. 1): III50– 7. 28 Jones PH. Statins as the cornerstone of drug therapy for dyslipidemia: monotherapy and combination therapy options. Am Heart J 2004; 148 (1 Suppl.): S9– 13. 29 Van Heek M, France CF, Compton DS et al. In vivo metabolism-based discovery of a potent cholesterol absorption inhibitor, SCH58235, in the rat and rhesus monkey through the identification of the active metabolites of SCH48461. J Pharmacol Exp Ther 1997; 283: 157– 63. 30 Knopp RH, Gitter H, Truitt T et al. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J 2003; 24: 729– 41. 31 Knopp RH, Dujovne CA, Le Beaut A, Lipka LJ, Suresh R, Veltri EP. Evaluation of the efficacy, safety, and tolerability of ezetimibe in primary hypercholesterolaemia: a pooled analysis from two controlled phase III clinical studies. Int J Clin Pract 2003; 57: 363– 8. 32 Bays HE, Moore PB, Drehobl MA et al. Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies. Clin Ther 2001; 23: 1209– 30. 33 Dujovne CA, Ettinger MP, McNeer JF 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– 7. 34 Gagne C, Bays HE, Weiss SR 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– 91. 35 Ballantyne CM, Houri J, Notarbartolo A et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation 2003; 107: 2409– 15. 36 Melani L, Mills R, Hassman D 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– 28. 37 Davidson MH, McGarry T, Bettis R et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol 2002; 40: 2125– 34. 38 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– 9. 39 Bays HE, Ose L, Fraser N et al. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther 2004; 26: 1758– 73. 40 Farnier M, Volpe M, Massaad R, Davies MJ, Allen C. Effect of co-administering ezetimibe with on-going simvastatin treatment on LDL-C goal attainment in hypercholesterolemic patients with coronary heart disease. Int J Cardiol 2005; 102: 327– 32. 41 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: 464– 73. 42 Vytorin (ezetimibe/simvastatin) tablet, MERCK/Schering-Plough Pharmaceuticals. North Wales, PA, 2004 (prescriber information). 43 Ose L, Shah A, Davies MJ et al. Consistency of lipid-altering effects of ezetimibe/simvastatin across gender, race, age, baseline low density lipoprotein cholesterol levels, and coronary heart disease status: results of a pooled retrospective analysis. Curr Med Res Opin 2006; 22: 823– 35. 44 Farnier M, Roth E, Gil-Extremera B et al. Efficacy and safety of the coadministration of ezetimibe/simvastatin with fenofibrate in patients with mixed hyperlipidemia. Am Heart J 2007; 153: 335– 8. 45 Feldman T, Koren M, Insull W Jr 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– 6. 46 Patel JV, Hughes EA. Efficacy, safety and LDL-C goal attainment of ezetimibe 10 mg-simvastatin 20 mg vs. placebo-simvastatin 20 mg in UK-based adults with coronary heart disease and hypercholesterolaemia. Int J Clin Pract 2006; 60: 914– 21. 47 Brohet C, Banai S, Alings AM, Massaad R, Davies MJ, Allen C. LDL-C goal attainment with the addition of ezetimibe to ongoing simvastatin treatment in coronary heart disease patients with hypercholesterolemia. Curr Med Res Opin 2005; 21: 571– 8. 48 Rosenson RS. Myocardial injury: the acute phase response and lipoprotein metabolism. J Amer Coll Cardiol 1993; 22: 933– 40. 49 Barrios V, Amabile N, Paganelli F et al. Lipid-altering efficacy of switching from atorvastatin 10 mg/day to ezetimibe/simvastatin 10/20 mg/day compared to doubling the dose of atorvastatin in hypercholesterolaemic patients with atherosclerosis or coronary heart disease. Int J Clin Pract 2005; 59: 1377– 86. 50 Constance C, Westphal S, Chung N et al. Efficacy of ezetimibe/simvastatin 10/20 and 10/40 mg compared with atorvastatin 20 mg in patients with type 2 diabetes mellitus. Diabetes Obes Metab 2007; 9: 575– 84. 51 Gaudiani LM, Lewin A, Meneghini L et al. Efficacy and safety of ezetimibe co-administered with simvastatin in thiazolidinedione-treated type 2 diabetic patients. Diabetes Obes Metab 2005; 7: 88– 97. 52 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499– 502. 53 Myers GL, Cooper GR, Winn CL, Smith SJ. The Centers for Disease Control-National Heart, Lung and Blood Institute Lipid Standardization Program. An approach to accurate and precise lipid measurements. Clin Lab Med 1989; 9: 105– 35. 54 Kiss Z, Simo IE, Ooi TC, Meuffels M, Hindmarsh JT. Presence of unsedimented precipitate in visually non-turbid supernates in the heparin–manganese method for HDL-cholesterol quantitation. Clin Biochem 1986; 19: 209– 11. 55 Warnick GR, Albers JJ. A comprehensive evaluation of the heparin–manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res 1978; 19: 65– 76. 56 Spencer FA, Goldberg RJ, Gore JM et al. Comparison of utilization of statin therapy at hospital discharge and six-month outcomes in patients with an acute coronary syndrome and serum low-density lipoprotein ≥ 100 mg/dl versus < 100 mg/dl. Am J Cardiol 2007; 100: 913– 8. 57 Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol 1998; 81: 582– 7. 58 Davidson MH, Palmisano J, Wilson H, Liss C, Dicklin MR. A multicenter, randomized, double-blind clinical trial comparing the low-density lipoprotein cholesterol-lowering ability of lovastatin 10, 20, and 40 mg/day with fluvastatin 20 and 40 mg/day. Clin Ther 2003; 25: 2738– 53. 59 Kiortsis DN, Giral P, Bruckert E, Turpin G. Factors associated with low compliance with lipid-lowering drugs in hyperlipidemic patients. J Clin Pharm Ther 2000; 25: 445– 51. 60 Black DM, Bakker-Arkema RG, Nawrocki JW. An overview of the clinical safety profile of atorvastatin (lipitor), a new HMG-CoA reductase inhibitor. Arch Intern Med 1998; 158: 577– 84. 61 Brewer HB Jr. Benefit-risk assessment of rosuvastatin 10 to 40 mg. Am J Cardiol 2003; 92: 23K– 9K. 62 Knopp RH. Drug treatment of lipid disorders. N Engl J Med 1999; 341: 498– 511. 63 Catapano AL, Davidson MH, Ballantyne CM et al. Lipid-altering efficacy of the ezetimibe/simvastatin single tablet versus rosuvastatin in hypercholesterolemic patients. Curr Med Res Opin 2006; 22: 2041– 53. 64 Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383– 9. 65 Kastelein J, Sager P, De Groot E, Veltri E. The ENHANCE trial: ezetimibe and simvastatin in hypercholesterolemia enhances atherosclerosis regression. Atherosclerosis 2003; 4: 341. 66 Rossebo A, Pedersen T, Skjaerpe T, Mitchel Y, Larsen V. Design of the simvastatin and ezetimibe in aortic stenosis (SEAS) study. Atherosclerosis 2003; 4: 253. Citing Literature Volume62, Issue4April 2008Pages 539-554 ReferencesRelatedInformation
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