title: Association of spironolactone use with all-cause mortality in heart failure: a propensity scored cohort study.
abstract: BACKGROUND
  In 3 randomized controlled trials in heart failure (HF), mineralocorticoid receptor antagonists reduced mortality. The net benefit from randomized controlled trials may not be generalizable, and eplerenone was, but spironolactone was not, studied in mild HF. We tested the hypothesis that spironolactone is associated with reduced mortality also in a broad unselected contemporary population with HF and reduced ejection fraction, in particular New York Heart Association (NYHA) I-II.
  
  
  RESULTS
  We prospectively studied 18 852 patients (age 71±12 years; 28% women) with NYHA I-IV and ejection fraction <40% who were registered in the Swedish Heart Failure Registry between 2000 and 2012 and who were (n=6551) or were not (n=12 301) treated with spironolactone. We derived propensity scores for spironolactone treatment based on 41 covariates. We assessed survival by Cox regression with adjustment for propensity scores and with matching based on propensity score. We performed sensitivity and residual confounding analyses and analyzed the NYHA I-II and III-IV subgroups separately. One-year survival was 83% versus 84% in treated versus untreated patients (log rank P<0.001). After adjustment for propensity scores, the hazard ratio for spironolactone was 1.05 (95% confidence interval, 1.00-1.11; P=0.054). Spironolactone interacted with NYHA (P<0.001). In the NYHA I-II subgroup, after adjustment for propensity scores, the hazard ratio for spironolactone was 1.11 (95% confidence interval, 1.02-1.21; P=0.019).
  
  
  CONCLUSIONS
  In an unselected contemporary population of HF with reduced ejection fraction, spironolactone was not associated with reduced mortality. The net benefits of spironolactone may be lower outside the clinical trial setting and in milder HF.
authors: Department of Medicine, Karolinska Institutet, Stockholm, Sweden. mail lars.lund@alumni.duke.edu
authors: Lars H
authors: LH
authors: Lund
authors: Bodil
authors: B
authors: Svennblad
authors: Håkan
authors: H
authors: Melhus
authors: Pär
authors: P
authors: Hallberg
authors: Ulf
authors: U
authors: Dahlström
authors: Magnus
authors: M
authors: Edner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D057216:Propensity Score; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D012720:Severity of Illness Index; D013148:Spironolactone / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone