Efficacy and safety of spironolactone in the heart failure with mid-range ejection fraction and heart failure with preserved ejection fraction A meta-analysis of randomized clinical trials

Background: Recent studies have shown the efficacy for using spironolactone to treat heart failure with reduced ejection fraction (HFrEF), but the efficacy of spironolactone for heart failure with mid-range ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) is unclear. This meta-analysis investigated the efficacy and safety of spironolactone in patients with HFmrEF and HFpEF. Methods and results: We searched several databases including PubMed and the Cochrane Collaboration, for randomized controlled trials (RCTs) that assessed spironolactone treatment in HFmrEF and HFpEF. Eleven RCTs including 4539 patients were included. Spironolactone reduced hospitalizations (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.73-0.95; P=.006), improved New York Heart Association functional classifications (NYHA-FC) (OR, 0.35; 95% CI, 0.19-0.66; P=.001), decreased the levels of brain natriuretic peptide (BNP) (mean difference [MD], -44.80pg/mL; 95% CI, -73.44--16.17; P=.002), procollagen type I C-terminal propeptide (PICP) (MD, -27.04 ng/mL; 95% CI, -40.77--13.32, P<.001) in HFmrEF and HFpEF. Besides, it improved 6-minute walking distances (6-MWD) (standard weighted mean difference [SMD], 0.45 m; 95% CI, 0.27-0.64; P<.001), decreased amino-terminal peptide of procollagen type-III (PIIINP) (SMD, -0.37mg/L; 95% CI, -0.59--0.15; P=.001) in HFpEF only. The risks of hyperkalemia (P<.001) and gynecomastia (P<.001) were increased. Conclusion: Patients with HFmrEF and HFpEF could benefit from spironolactone treatment, with reduced hospitalizations, BNP levels, improved NYHA-FC, alleviated myocardial fibrosis by decreasing serum PICP in HFmrEF and HFpEF, decreased PIIINP levels and increased 6-MWD only in HFpEF. The risks of hyperkalemia and gynecomastia were significantly increased with the spironolactone treatment.