title: 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.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Heidelberg, Heidelberg, Germany, Lutz.Frankenstein@med.uni-heidelberg.de.
authors.forename: L
authors.initials: L
authors.lastname: Frankenstein
authors.forename: H A
authors.initials: HA
authors.lastname: Katus
authors.forename: M
authors.initials: M
authors.lastname: Grundtvig
authors.forename: T
authors.initials: T
authors.lastname: Hole
authors.forename: J
authors.initials: J
authors.lastname: de Blois
authors.forename: D
authors.initials: D
authors.lastname: Schellberg
authors.forename: D
authors.initials: D
authors.lastname: Atar
authors.forename: C
authors.initials: C
authors.lastname: Zugck
authors.forename: S
authors.initials: S
authors.lastname: Agewall
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009664:Norway; D057216:Propensity Score; D016016:Proportional Hazards Models; D013148:Spironolactone / Q000008:administration & dosage / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D013148:Spironolactone