European Journal of Clinical Pharmacology

, Volume 69, Issue 10, pp 1747–1755 | Cite as

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

  • L. Frankenstein
  • H. A. Katus
  • M. Grundtvig
  • T. Hole
  • J. de Blois
  • D. Schellberg
  • D. Atar
  • C. Zugck
  • S. Agewall
  • on behalf of the Norwegian Heart Failure Registry steering committee
Clinical Trial



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.


Chronic heart failure Spironolactone Mineralocorticoid receptor antagonists Beta-blocker Survival Mortality benefit Combination therapy 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • L. Frankenstein
    • 3
    • 6
  • H. A. Katus
    • 3
  • M. Grundtvig
    • 4
  • T. Hole
    • 5
  • J. de Blois
    • 2
  • D. Schellberg
    • 3
  • D. Atar
    • 1
  • C. Zugck
    • 3
  • S. Agewall
    • 1
  • on behalf of the Norwegian Heart Failure Registry steering committee
    • 4
  1. 1.Department of Cardiology, Oslo University Hospital, Ulleval and Institute of Clinical SciencesUniversity of OsloOsloNorway
  2. 2.Centre Hospitalier Universitaire Affilié de QuébecQuebecCanada
  3. 3.University of HeidelbergHeidelbergGermany
  4. 4.Medical Department LillehammerLillehammerNorway
  5. 5.Medical Faculty, Norwegian University of Science and Technology (NTNU), Trondheim, Norway & Medical ClinicHelse Møre and Romsdal HFÅlesundNorway
  6. 6.Department of Cardiology, Angiology, PulmonologyUniversity of HeidelbergHeidelbergGermany

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