Results of the Randomized Aldosterone Antagonism in Heart Failure with Preserved Ejection Fraction trial (RAAM-PEF)

J Card Fail. 2011 Aug;17(8):634-42. doi: 10.1016/j.cardfail.2011.04.007. Epub 2011 May 31.

Abstract

Background: Cardiac fibrosis is a major determinant of myocardial stiffness, diastolic dysfunction, and heart failure (HF). By reducing cardiac fibrosis, aldosterone antagonists have the potential to be beneficial in heart failure with preserved ejection fraction (HFpEF).

Methods and results: In a randomized, double-blind, placebo-controlled trial of 44 patients with HFpEF, we examined the effects of eplerenone, an aldosterone antagonist, on changes in 6-minute walk distance (primary end point), diastolic function, and biomarkers of collagen turnover (secondary end points). All patients had a history of hypertension, 61% were diabetic, and 52% had prior HF hospitalization. After 6 months of treatment, similar improvements in 6 minute walk distance were noted in the eplerenone and placebo groups (P = .91). However, compared with placebo, eplerenone was associated with a significant reduction in serum markers of collagen turnover (procollagen type I aminoterminal peptide, P = .009 and carboxy-terminal telopeptide of collagen type I, P = .026) and improvement in echocardiographic measures of diastolic function (E/E', P = .01).

Conclusions: Although eplerenone was not associated with an improvement in exercise capacity compared to placebo, it was associated with significant reduction in markers of collagen turnover and improvement in diastolic function. Whether these favorable effects will translate into morbidity and mortality benefit in HFpEF remains to be determined.

Trial registration: ClinicalTrials.gov NCT00108251.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Collagen / blood
  • Double-Blind Method
  • Eplerenone
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology*
  • Humans
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Spironolactone / analogs & derivatives*
  • Spironolactone / pharmacology
  • Spironolactone / therapeutic use
  • Stroke Volume / drug effects
  • Stroke Volume / physiology*

Substances

  • Biomarkers
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Eplerenone
  • Collagen

Associated data

  • ClinicalTrials.gov/NCT00108251