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

Objective: To evaluate the efficacy and safety of soluble guanylate cyclase (sGC) stimulators in patients with heart failure (HF). Methods: A systematic literature search from several electronic databases (Web of Science, PubMed, Embase, Medline) was performed up until March 2021. Eligible studies included randomized controlled trials (RCTs) that compared sGC stimulators treatment with placebo. Data extracted from eligible RCTs were pooled using relative risk (RR) and weight mean difference (WMD) on random effect model or fixed effect model. Results: A total of eight RCTs involving 7225 patients met the inclusion criteria. For the efficacy endpoint, sGC stimulators significantly reduced HF-related hospitalization or cardiovascular (CV) death (RR = 0.92, 95%CI: 0.86-0.99; P = 0.03), but no relationship was found for 6-minute walking distance (6MWD) (SMD = 0.04, 95%CI:-0.09-0.17; P = 0.55). In addition, compared to control group, the change of NT-proBNP was statistically decreased in the riociguat group (SMD =-0.78, 95%CI:-1.09--0.47; P < 0.00), yet not in vericiguat group (SMD = 0.05, 95%CI:-0.19-0.28; P = 0.70). For the safety endpoint, there was no significant difference in all-cause mortality (RR = 0.98 95%CI: 0.88-1.09; P = 0.69) and serious adverse events (RR = 0.95, 95%CI: 0.892-1.02; P = 0.16) between SGC stimulants group and control group. Conclusion: The oral therapy with sGC stimulators including vericiguat and riociguat decreases the incidence of HF-related hospitalization or CV death with good tolerability and safety. The study did not support improvement in many parameters including 6MWD and NT-proBNP in HF patients.