The efficacy and safety of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis

Medicine (Baltimore). 2018 Oct;97(41):e12709. doi: 10.1097/MD.0000000000012709.

Abstract

Background: Several randomized controlled trials (RCTs) have been investigated the benefits of soluble guanylate cyclase (sGC) stimulators in the treatment of heart failure, but a comprehensive evaluation is lacking. We performed a meta-analysis to evaluate the efficacy and safety of oral sGC stimulators (vericiguat and riociguat) in patients with heart failure.

Methods: Studies were searched and screened in PubMed, Embase, and Cochrane Library. Eligible RCTs were included that reported mortality, the change of EuroQol Group 5-Dmensional Self-report Questionnaire (EQ-5D) US index, N-terminal pro-B-type natriuretic peptide (NT-proBNP), or serious adverse events (SAEs). Relative risk or weight mean difference (WMD) was estimated using fixed effect model or random effect model. Analysis of sensitivity and publication bias was conducted.

Results: Five trials with a total of 1200 patients were included. sGC stimulators had no impact on the mortality (1.25; 95% confidence interval 0.50-3.11) and significantly improved EQ-5D US index (0.04; 95% confidence interval 0.020-0.05). Furthermore, in comparison with control group, NT-proBNP was statistically decreased in riociguat group (-0.78; 95% confidence interval -1.01 to -0.47), but not in vericiguat group (0.04, 95% confidence interval -0.18 to 0.25). There were not obverse differences in SAEs between sGC stimulators and control groups (0.90; 95% confidence interval 0.72-1.12).

Conclusion: Our meta-analysis suggests that sGC stimulators could improve the quality of life in patients with heart failure with good tolerance and safety, but their long-term benefits need to be observed in the future. sGC stimulators are likely to be promising add-on strategies for the treatment of heart failure.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Enzyme Activators / administration & dosage
  • Enzyme Activators / adverse effects
  • Enzyme Activators / therapeutic use*
  • Female
  • Heart Failure / drug therapy*
  • Heterocyclic Compounds, 2-Ring / administration & dosage
  • Heterocyclic Compounds, 2-Ring / adverse effects
  • Heterocyclic Compounds, 2-Ring / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / biosynthesis
  • Peptide Fragments / biosynthesis
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Quality of Life
  • Soluble Guanylyl Cyclase / biosynthesis*

Substances

  • Enzyme Activators
  • Heterocyclic Compounds, 2-Ring
  • Peptide Fragments
  • Pyrazoles
  • Pyrimidines
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Soluble Guanylyl Cyclase
  • vericiguat
  • riociguat