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

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.