title: Influence of ejection fraction on outcomes and efficacy of spironolactone in patients with heart failure with preserved ejection fraction.
abstract: OBJECTIVE
  While mineralocorticoid receptor antagonists (MRAs) have been shown to benefit patients with reduced left ventricular ejection fraction (LVEF), spironolactone did not reduce the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest in patients with heart failure with preserved ejection fraction (HFpEF) in the TOPCAT trial, which enrolled patients with LVEF of 45% or greater. We utilized data from TOPCAT to assess the relationship between LVEF as well as outcomes and efficacy of spironolactone.
  
  
  RESULTS
  We assessed differences in baseline characteristics and outcomes across LVEF categories in 3444 patients with HFpEF, and determined whether LVEF modified the treatment effect of spironolactone. Ejection fraction ranged from 44 to 85%. Patients with higher ejection fraction were older, more likely to be female, less likely to have a history of myocardial infarction, and more likely to have a history of hypertension and diabetes. The incidence of the primary endpoint and cardiovascular death was highest in patients at the lower end of the ejection fraction spectrum. Ejection fraction modified the spironolactone treatment effect, particularly in the patients enrolled in the Americas, for the primary outcome (P = 0.046) and for heart failure hospitalization (P = 0.039), with stronger estimated benefits of spironolactone at the lower end of the ejection fraction spectrum with respect to the primary endpoint (LVEF <50%: HR 0.72, 95% CI 0.50, 1.05; LVEF ≥60%: HR 0.97, 95% CI 0.76, 1.23) and heart failure hospitalization (LVEF <50%: HR 0.76, 95% CI 0.46, 1.27; LVEF ≥60%: HR 0.98, 95% CI 0.74, 1.30).
  
  
  CONCLUSIONS
  In patients with HFpEF enrolled in TOPCAT, patient characteristics and outcomes varied substantially by LVEF. The potential efficacy of spironolactone was greatest at the lower end of the LVEF spectrum.
  NCT00094302.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA ssolomon@rics.bwh.harvard.edu.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Claggett
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
authors.forename: Eldrin F
authors.initials: EF
authors.lastname: Lewis
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
authors.forename: Akshay
authors.initials: A
authors.lastname: Desai
authors.affiliation: Minneapolis VA Hospital, Minneapolis, MN, USA.
authors.forename: Inder
authors.initials: I
authors.lastname: Anand
authors.affiliation: University of Arizona, Tuscon, AZ, USA.
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Sweitzer
authors.affiliation: Montreal Heart Institute, Montreal, Canada.
authors.forename: Eileen
authors.initials: E
authors.lastname: O'Meara
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Sanjiv J
authors.initials: SJ
authors.lastname: Shah
authors.affiliation: New England Research Institute, Watertown, MA, USA.
authors.forename: Sonja
authors.initials: S
authors.lastname: McKinlay
authors.affiliation: National Heart, Lung and Blood Institute, Bethesda, MD, USA.
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Fleg
authors.affiliation: National Heart, Lung and Blood Institute, Bethesda, MD, USA.
authors.forename: George
authors.initials: G
authors.lastname: Sopko
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D013148:Spironolactone / Q000008:administration & dosage*; D013318:Stroke Volume / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone
keywords: Heart failure with preserved ejection fraction; Spironolactone