Association between spironolactone added to beta-blockers and ACE inhibition and survival in heart failure patients with reduced ejection fraction: a propensity score-matched cohort study
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Heart failure (CHF) guidelines recommend mineralocorticoid receptor antagonists for all symptomatic patients treated with a combination of ACE inhibitors/angiotensin receptor blockers (ARBs) and beta-blockers. As opposed to both eplerenone trials, patients in RALES (spironolactone) received almost no beta-blockers. Since pharmacological properties differ between eplerenone and spironolactone, the prognostic benefit of spironolactone added to this baseline combination therapy needs clarification.
We included 4,832 CHF patients with chronic systolic dysfunction from the Norwegian Heart Failure Registry and the heart failure outpatients’ clinic of the University of Heidelberg. Propensity scores for spironolactone receipt were calculated for each patient and used for matching to patients without spironolactone.
During a total follow-up of 17,869 patient-years, 881 patients (27.0 %) died in the non-spironolactone group and 445 (28.4 %) in the spironolactone group. Spironolactone was not associated with improved survival, neither in the complete sample (HR 0.82; 95 % CI 0.64–1.07; HR 1.03; 95 % CI 0.88–1.20; multivariate and propensity score adjusted respectively), nor in the propensity-matched cohort (HR 0.98; 95 % CI 0.82–1.18).
In CHF outpatients we were unable to observe an association between the use of spironolactone and improved survival when administered in addition to a combination of ACE/ARB and beta-blockers.
KeywordsChronic heart failure Spironolactone Mineralocorticoid receptor antagonists Beta-blocker Survival Mortality benefit Combination therapy
- 1.McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P (2012) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 33(14):1787–1847PubMedCrossRefGoogle Scholar
- 2.Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW (2009) 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 119(14):e391–e479PubMedCrossRefGoogle Scholar
- 4.Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348(14):1309–1321. doi: 10.1056/NEJMoa030207 PubMedCrossRefGoogle Scholar
- 5.Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341(10):709–717. doi: 10.1056/NEJM199909023411001 PubMedCrossRefGoogle Scholar
- 10.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 (2008) 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 Heart J 29(19):2388–2442PubMedCrossRefGoogle Scholar
- 12.Love TE (2009) Using propensity scores: stratification, adjustment, sensitivity and strategies. http://www.chrp.org/propensity/. Accessed 4 June 2005
- 17.Love TE (2008) Spreadsheet-based sensitivity analysis calculations for matched samples. Center for Health Care Research & Policy, Case Western Reserve University, ClevelandGoogle Scholar
- 20.Masoudi FA, Gross CP, Wang Y, Rathore SS, Havranek EP, Foody JM, Krumholz HM (2005) Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States, 1998–2001. Circulation 112(1):39–47. doi: 10.1161/CIRCULATIONAHA.104.527549 PubMedCrossRefGoogle Scholar
- 23.Fonarow GC, Alber NM, Curtis AB, Gheorghiade M, Liu Y, Mehra MR, O’Conor CM, Reynolds D, Walsh MN, Yancy CW (2012) Incremental reduction in risk of death associated with use of guideline-recommended therapies in patients with heart failure: a nested case–control analysis of improve HF. J Am Heart Assoc 1:16–20. doi: 10.1161/JAHA.111.000018 PubMedGoogle Scholar
- 26.Hamaguchi S, Kinugawa S, Tsuchihashi-Makaya M, Goto K, Goto D, Yokota T, Yamada S, Yokoshiki H, Takeshita A, Tsutsui H (2010) Spironolactone use at discharge was associated with improved survival in hospitalized patients with systolic heart failure. Am Heart J 160(6):1156–1162PubMedCrossRefGoogle Scholar