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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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Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusion

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.

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Authors and Affiliations

  1. Department of Cardiology, Oslo University Hospital, Ulleval and Institute of Clinical Sciences, University of Oslo, Oslo, Norway

    D. Atar & S. Agewall

  2. Centre Hospitalier Universitaire Affilié de Québec, Quebec, Canada

    J. de Blois

  3. University of Heidelberg, Heidelberg, Germany

    L. Frankenstein, H. A. Katus, D. Schellberg & C. Zugck

  4. Medical Department Lillehammer, Lillehammer, Norway

    M. Grundtvig

  5. Medical Faculty, Norwegian University of Science and Technology (NTNU), Trondheim, Norway & Medical Clinic, Helse Møre and Romsdal HF, Ålesund, Norway

    T. Hole

  6. Department of Cardiology, Angiology, Pulmonology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    L. Frankenstein

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  1. L. Frankenstein
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on behalf of the Norwegian Heart Failure Registry steering committee

Corresponding author

Correspondence to L. Frankenstein.

Additional information

D. Atar, C. Zugck, and S. Agewall contributed equally

M. Grundtvig and T. Holstein - on behalf of the Norwegian Heart Failure Registry steering committee

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Frankenstein, L., Katus, H.A., Grundtvig, M. et al. 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. Eur J Clin Pharmacol 69, 1747–1755 (2013). https://doi.org/10.1007/s00228-013-1512-x

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  • DOI: https://doi.org/10.1007/s00228-013-1512-x

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