title: Rationale and design of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction.
abstract: BACKGROUND
  Despite increasing prevalence of heart failure (HF) in patients with preserved ejection fraction (PEF), there are no available therapies proven to reduce morbidity and mortality. Aldosterone, a potent stimulator of myocardial and vascular fibrosis, may be a key mediator of HF progression in this population and is therefore an important therapeutic target.
  
  
  OBJECTIVE
  The TOPCAT trial is designed to evaluate the effect of spironolactone, an aldosterone antagonist, on morbidity, mortality, and quality of life in patients with HF-PEF.
  
  
  METHODS
  Up to 3,515 patients with HF-PEF will be randomized in double-blind fashion to treatment with spironolactone (target dose 30 mg daily) or matching placebo. Eligible patients include those with age ≥50 years, left ventricular ejection fraction ≥45%, symptomatic HF, and either a hospitalization for HF within the prior year or an elevated natriuretic peptide level (B-type natriuretic peptide ≥100 pg/mL or N-terminal pro-B-type natriuretic peptide ≥360 pg/mL) within the 60 days before randomization. Patients with uncontrolled hypertension and those with known infiltrative or hypertrophic cardiomyopathy are excluded. The primary end point is the composite of cardiovascular death, hospitalization for HF, or aborted cardiac arrest. Key secondary end points include quality of life, nonfatal cardiovascular events, and new-onset atrial fibrillation. Ancillary studies of echocardiography, tonometry, and cardiac biomarkers will provide more insight regarding this understudied population and the effects of spironolactone therapy.
  
  
  CONCLUSIONS
  TOPCAT is designed to assess definitively the role of spironolactone in the management of HF-PEF.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA. adesai@partners.org
authors.forename: Akshay S
authors.initials: AS
authors.lastname: Desai
authors.forename: Eldrin F
authors.initials: EF
authors.lastname: Lewis
authors.forename: Rebecca
authors.initials: R
authors.lastname: Li
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Susan F
authors.initials: SF
authors.lastname: Assmann
authors.forename: Robin
authors.initials: R
authors.lastname: Boineau
authors.forename: Nadine
authors.initials: N
authors.lastname: Clausell
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Fleg
authors.forename: Ivan
authors.initials: I
authors.lastname: Gordeev
authors.forename: Sonja
authors.initials: S
authors.lastname: McKinlay
authors.forename: Eileen
authors.initials: E
authors.lastname: O'Meara
authors.forename: Tamaz
authors.initials: T
authors.lastname: Shaburishvili
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
mesh_terms: D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D011788:Quality of Life; D012107:Research Design; D013148:Spironolactone / Q000627:therapeutic use*; D013318:Stroke Volume
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone