Aldosterone antagonists improve ejection fraction and functional capacity independently of functional class: a meta-analysis of randomised controlled trials

Context Current guidelines recommend the use of aldosterone antagonists (AA) in patients with moderately severe to severe symptoms New York Heart Association (NYHA) class III to IV and systolic heart failure. Objective To determine the efficacy of AA in improving ejection fraction (EF) and functional capacity and to assess whether this effect was influenced by baseline NYHA classification. Study design Meta-analysis of randomized controlled trials. Data extraction performed independently by two researchers. Data Sources MEDLINE and the Cochrane Library. Study Selection Prospective randomized controlled trials using AA were included if there was a clear description of the baseline NYHA classification and change in EF in patients from study initiation to completion. Results Data from 1,575 patients enrolled in fourteen studies were included. Overall, there was a weighted mean improvement in EF of 3.2% and in NYHA classification of 0.13 in subjects treated with AA when compared to controls (p<0.001). A mixed effects meta-regression analysis revealed that baseline NYHA was not predictive of improvement in EF (p=0.67) nor NYHA status (p=0.18). Conclusions The results of this meta-analysis suggest that AA is associated with significant improvements in EF and functional class independent of baseline functional capacity. This supports and expands on the recently published EMPHASIS-HF trial and suggests that the current restriction of AA use to patients with NYHA class III-IV symptoms should be reconsidered.