oBjECTIVES: To summarize the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) compared with placebo for the treatment of heart failure with reduced ejection fraction (HFrEF) by assessing clinically relevant end points of randomized controlled trials.
METhoDS: The Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, ACP Journal Club, DARE and International Pharmaceutical Abstracts databases were searched from inception to June 2014. Three authors independently reviewed and identified relevant articles. Included were randomized, doubleblinded, placebo-controlled trials that investigated spironolactone or eplerenone in adult patients with HFrEF regardless of etiology or symptomatology.
RESulTS: The search strategy identified 726 articles; three met the inclusion criteria and included a total of 11,032 participants. The primary outcome of death from any cause was statistically significantly reduced with MRAs over placebo (risk ratio [RR] 0.81 [95% CI 0.74 to 0.88]; P<0.001). Hyperkalemia (serum potassium ≥6.0 mmol/L) was significantly higher with MRA therapy (RR 1.41 [95% CI 1.16 to 1.72]; P<0.001). Other clinically relevant safety outcomes were not consistently reported. With respect to efficacy, MRAs reduced cardiovascular mortality (RR 0.80 [95% CI 0.73 to 0.87]; P<0.001) and hospitalizations due to heart failure (RR 0.76 [95% CI 0.64 to 0.90]; P=0.001), but not all-cause hospitalization (RR 0.91 [95% CI 0.79 to 1.06]; P=0.23).
CoNCluSIoNS: The present review highlights the benefit of MRAs across the spectrum of HFrEF despite a higher incidence of hyperkalemia. Therefore, MRA therapy should not be withheld from appropriately selected patients with HFrEF because the risk of adverse events does not appear to exceed the overall benefit in mortality reduction.
