title: The Impact Exerted on Clinical Outcomes of Patients With Chronic Heart Failure by Aldosterone Receptor Antagonists: A Meta-Analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  Aldosterone receptor antagonists (ARAs) have been associated with improved clinical outcomes in patients with heart failure with reduced left ventricular ejection fraction (HFREF), but not in those with heart failure with preserved left ventricular ejection fraction (HFpEF). With the aim to study this topic more deeply, we carried out a meta-analysis of selective and non-selective ARAs in HFREF and HFpEF.
  
  
  METHODS
  We searched PubMed and Scopus databases. We decided to incorporate in the meta-analysis only randomized controlled trials (RCTs) of ARAs in patients with chronic heart failure (CHF) if they met the following criteria: experimental groups included patients with CHF treated with ARAs in addition to the conventional therapy; control groups included patients with CHF receiving conventional therapy without ARAs. Outcomes of interest were all-cause death, hospitalizations from cardiovascular cause, hyperkalemia, or gynecomastia.
  
  
  RESULTS
  We detected 15 studies representing 15,671 patients. ARAs were associated with a reduced odds of all-cause death (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.73 - 0.87) and hospitalizations from cardiovascular cause (OR: 0.73; 95% CI: 0.61 - 0.89). However, subgroup analysis showed that these advantages were limited to HFREF (all-cause death: OR: 0.77, 95% CI: 0.69 - 0.84; hospitalizations from cardiovascular cause: OR: 0.66, 95% CI: 0.51 - 0.85), but they did not affect the HFpEF group (all-cause death: OR: 0.91, 95% CI: 0.76 - 1.1; hospitalizations from cardiovascular cause: OR: 0.85, 95% CI: 0.7 - 1.09). ARAs increased the risk of hyperkalemia (OR: 2.17; 95% CI: 1.88 - 2.5). Non-selective ARAs, but not selective ARAs, increased the risk of gynecomastia (OR: 8.22, 95% CI: 4.9 - 13.81 vs. OR: 0.74, 95% CI: 0.43 - 1.27).
  
  
  CONCLUSIONS
  ARAs reduced the risk of adverse cardiac events in HFREF but not HFpEF. In particular, ARA use in HFpEF patients is questionable, since in this CHF type, no significant improvement in all-cause death and cardiovascular hospitalizations was demonstrated with ARA treatment, in the face of the well-known risks of hyperkalemia and/or gynecomastia that chronic ARA therapy entails. Selective ARAs were equally effective as non-selective ARAs, without the risk of gynecomastia.
authors.affiliation: Cardiology Unit, Presidio Sanitario Intermedio "Elena d'Aosta", ASL Napoli 1 Centro, Napoli, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: De Vecchis
authors.affiliation: Cardiology Unit, Presidio Sanitario Intermedio "Elena d'Aosta", ASL Napoli 1 Centro, Napoli, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cantatrione
authors.affiliation: Cardiology Unit, Presidio Sanitario Intermedio "Elena d'Aosta", ASL Napoli 1 Centro, Napoli, Italy.
authors.forename: Damiana
authors.initials: D
authors.lastname: Mazzei
authors.affiliation: Division of Sports Medicine, Presidio Sanitario Intermedio "Elena d'Aosta", ASL Napoli 1 Centro, Napoli, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Barone
authors.affiliation: Division of Cardiology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione Giovanni Pascale" IRCCS, Napoli, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Maurea
keywords: Aldosterone receptor antagonists; Heart failure; Heart failure with preserved ejection fraction; Heart failure with reduced ejection fraction; Meta-analysis