Rationale and design of the eplerenone in mild patients hospitalization and survival study in heart failure (EMPHASIS-HF)

European Journal of Heart Failure

Volumn 12, Issue 6, 2010, Pages 617-622

  Zannad, Faiez ^a   McMurray, John J V ^b   Drexler, Helmut ^c   Krum, Henry ^d   Van Veldhuisen, Dirk J ^e   Swedberg, Karl ^f   Shi, Harry ^g   Vincent, John ^g   Pitt, Bertram ^h  

^a INSERM   (France)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

^c HANNOVER MEDICAL SCHOOL   (Germany)

^d MONASH UNIVERSITY   (Australia)

^e UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^f UNIVERSITY OF GOTHENBURG   (Sweden)

^g PFIZER INC   (United States)

^h UNIVERSITY OF MICHIGAN   (United States)

Author keywords

Aldosterone antagonist; Clinical trial; Eplerenone; Outcome; Systolic heart failure

Indexed keywords

EPLERENONE; PLACEBO; POTASSIUM;

ACUTE HEART INFARCTION; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; FEMALE; GLOMERULUS FILTRATION RATE; HEART EJECTION FRACTION; HEART FAILURE; HEART LEFT VENTRICLE FAILURE; HEART VENTRICLE FUNCTION; HOSPITAL ADMISSION; HUMAN; MAJOR CLINICAL STUDY; MALE; MORBIDITY; MORTALITY; MULTICENTER STUDY; POTASSIUM BLOOD LEVEL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL;

ADRENERGIC BETA-ANTAGONISTS; ALDOSTERONE ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CHRONIC DISEASE; DOUBLE-BLIND METHOD; HEART FAILURE, SYSTOLIC; HOSPITALIZATION; HUMANS; RESEARCH DESIGN; SPIRONOLACTONE; SURVIVAL ANALYSIS;

EID: 77952962152     PISSN: 13889842     EISSN: 18790844     Source Type: Journal    
DOI: 10.1093/eurjhf/hfq049     Document Type: Article

References (29)

1. Funder JW. Reconsidering the roles of the mineralocorticoid receptor. Hypertension 2009;53:286-290.
2. Rocha R, Rudolph AE, Frierdich GE, Nachowiak DA, Kekec BK, Blomme EA, McMahon EG, Delyani JA. Aldosterone induces a vascular inflammatory pheno-type in the rat heart. Am J Physiol Heart Circ Physiol 2002;283:H1802-H1810.
3. Silvestre JS, Heymes C, Oubenaissa A, Robert V, Aupetit-Faisant B, Carayon A, Swynghedauw B, Delcayre C. Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis. Circulation 1999;99:2694-2701.
4. Delcayre C, Swynghedauw B. Molecular mechanisms of myocardial remodeling. The role of aldosterone. J Mol Cell Cardiol 2002;34:1577-1584.
5. Struthers AD. The clinical implications of aldosterone escape in congestive heart failure. Eur J Heart Fail 2004;6:539-545.
6. Sato A, Saruta T. Aldosterone breakthrough during angiotensin-converting enzyme inhibitor therapy. Am J Hypertens 2003;16:781-788.
7. Fung JW, Yu CM, Yip G, Chan S, Yandle TG, Richards AM, Nicholls MG, Sanderson JE. Effect of beta blockade (carvedilol or metoprolol) on activation of the renin-angiotensin-aldosterone system and natriuretic peptides in chronic heart failure. Am J Cardiol 2003;92:406-410.
8. McKelvie RS, Yusuf S, Pericak D, Avezum A, Burns RJ, Probstfield J, Tsuyuki RT, White M, Rouleau J, Latini R, Maggioni A, Young J, Pogue J. Comparison of can-desartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 1999;100:1056-1064.
9. Boccanelli A, Cacciatore G, Mureddu GF, de Simone G, Clemenza F, De Maria R, Di Lenarda A, Gavazzi A, Latini R, Masson S, Porcu M, Vanasia M, Gonzini L, Maggioni AP. Baseline characteristics of patients recruited in the AREA IN-CHF study (Antiremodelling Effect of Aldosterone Receptors Blockade with Canre-none in Mild Chronic Heart Failure). J Cardiovasc Med (Hagerstown) 2007;8: 683-691.
10. Cohn JN, Anand IS, Latini R, Masson S, Chiang YT, Glazer R. Sustained reduction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial. Circulation 2003;108:1306-1309.
11. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999;341:709-717.
12. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348: 1309-1321.
13. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Stromberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail 2008;10:933-989.
14. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353: 2001-2007.
15. Lakhdar R, Al-Mallah MH, Lanfear DE. Safety and tolerability of angiotensin-converting enzyme inhibitor versus the combination of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in patients with left ventricular dysfunction: a systematic review and meta-analysis of randomized controlled trials. J Card Fail 2008;14:181-188.
16. Williams RE. The effect of neurohormonal antagonists in reducing heart failure hospitalizations. Curr Med Res Opin 2006;22:139-150.
17. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions The SOLVD Investigators. N Engl J Med 1992;327:685-691.
18. Gustafsson F, Schou M, Videbaek L, Dridi N, Ryde H, Handberg J, Hildebrandt PR. Incidence and predictors of hospitalization or death in patients managed in multi-disciplinary heart failure clinics. Eur J Heart Fail 2009;11:413-419.
19. Solomon SD, Dobson J, Pocock S, Skali H, McMurray JJ, Granger CB, Yusuf S, Swedberg K, Young JB, Michelson EL, Pfeffer MA. Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Investigators. Influence of nonfatal hospitalization for heart failure on subsequent mortality in patients with chronic heart failure. Circulation 2007;116:1482-1487.
20. Wang NC, Maggioni AP, Konstam MA, Zannad F, Krasa HB, Burnett JC Jr, Grinfeld L, Swedberg K, Udelson JE, Cook T, Traver B, Zimmer C, Orlandi C, Gheorghiade M. Clinical implications of QRS duration in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction. JAMA 2008;299:2656-2666.
21. Boccanelli A, Mureddu GF, Cacciatore G, Clemenza F, Di Lenarda A, Gavazzi A, Porcu M, Latini R, Lucci D, Maggioni AP, Masson S, Vanasia M, de Simone G. Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results. Eur J Heart Fail 2009;11:68-76.
22. Chan AK, Sanderson JE, Wang T, Lam W, Yip G, Wang M, Lam YY, Zhang Y, Yeung L, Wu EB, Chan WW, Wong JT, So N, Yu CM. Aldosterone receptor antagonism induces reverse remodeling when added to angiotensin receptor blockade in chronic heart failure. J Am Coll Cardiol 2007;50:591-596.
23. Berry C, Murphy NF, De Vito G, Galloway S, Seed A, Fisher C, Sattar N, Vallance P, Hillis WS, McMurray J. Effects of aldosterone receptor blockade in patients with mild-moderate heart failure taking a beta-blocker. Eur J Heart Fail 2007;9:429-434.
24. Macdonald JE, Kennedy N, Struthers AD. Effects of spironolactone on endothelial function, vascular angiotensin converting enzyme activity, and other prognostic markers in patients with mild heart failure already taking optimal treatment. Heart 2004;90:765-770.
25. Ezekowitz JA, McAlister FA. Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials. Eur Heart J 2009;30: 469-477.
26. Udelson JE, Feldman AM, Greenberg B, Pitt B, Mukherjee R, Solomon HA, Konstam MA. Randomized, double-blind, multicenter, placebo-controlled study evaluating the effect of aldosterone antagonism with eplerenone on ventricular remodeling in patients with mild-to-moderate heart failure and left ventricular systolic dysfunction. Cir Heart Fail. Published online ahead of print 18 March 2010.
27. Levy DG, Rocha R, Funder JW. Distinguishing the antihypertensive and electrolyte effects of eplerenone. J Clin Endocrinol Metab 2004;89:2736-2740.
28. Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, Redelmeier DA. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004;351:543-551.
29. Weir RA, McMurray JJ, Puu M, Solomon SD, Olofsson B, Granger CB, Yusuf S, Michelson EL, Swedberg K, Pfeffer MA. Efficacy and tolerability of adding an angio-tensin receptor blocker in patients with heart failure already receiving an angiotensin-converting inhibitor plus aldosterone antagonist, with or without a beta blocker. Findings from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial. Eur J Heart Fail 2008;10:157-163.