Comparative efficacy and safety of mineralocorticoid receptor antagonists in heart failure: a network meta-analysis of randomized controlled trials

Heart Fail Rev. 2019 Sep;24(5):637-646. doi: 10.1007/s10741-019-09790-5.

Abstract

The efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure (HF) are controversial. To explore the role of MRAs in HF patients with an ejection fraction of no more than 45%, we conducted a network meta-analysis of randomized controlled trials (RCTs). We systematically searched PubMed, Embase, the Cochrane Library, and Clinicaltrials. RCTs involving the efficacy and/or safety of the use of MRAs in patients with HF were included. Outputs are presented as the surface under the cumulative ranking area (SUCRA) probabilities. Thirteen RCTs involving a total of 13,597 participants were included. Finerenone 10 mg was associated with the lowest probability of achieving at cardiovascular mortality (SUCRA, 5.0%), followed by finerenone 7.5 mg (SUCRA, 31.6%). In reducing N-terminal pro-B-type natriuretic peptide, finerenone 15 mg and finerenone 7.5 mg ranked the best and second best (SUCRA 68.1% and 63.8%, respectively), followed by finerenone 10 mg (SUCRA 59.2%). Spironolactone and canrenone have a higher risk of hyperkalemia and renal deterioration. Regarding the prevention of worsening renal function, finerenone 7.5 mg (SUCRA 14.3%) was the best treatment, followed by finerenone 2.5 mg (SUCRA 16.3%) and finerenone 10 mg (SUCRA 25.6%). Compared with spironolactone and eplerenone, finerenone 10 mg was associated with low risk in the occurrence of cardiovascular mortality, hospitalization, and adverse events (P < 0.01). This network meta-analysis is the first to find that finerenone 7.5-10 mg has the highest probability of being the optimal alternative among MRAs in the treatment of HF patients with an ejection fraction of no more than 45%.

Keywords: Heart failure; Hyperkalemia; Meta-analysis; Mineralocorticoid receptor antagonists.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Eplerenone / administration & dosage
  • Eplerenone / adverse effects
  • Eplerenone / therapeutic use*
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Hospitalization
  • Humans
  • Hyperkalemia / chemically induced
  • Mineralocorticoid Receptor Antagonists / administration & dosage
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Naphthyridines / administration & dosage
  • Naphthyridines / adverse effects
  • Naphthyridines / therapeutic use*
  • Natriuretic Peptide, Brain / blood
  • Network Meta-Analysis*
  • Peptide Fragments / blood
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency / chemically induced
  • Spironolactone / administration & dosage
  • Spironolactone / adverse effects
  • Spironolactone / therapeutic use*
  • Treatment Outcome

Substances

  • Mineralocorticoid Receptor Antagonists
  • Naphthyridines
  • Peptide Fragments
  • finerenone
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Spironolactone
  • Eplerenone