sGC Stimulators for Heart Failure: A Meta-Analysis of Randomized Controlled Trials

Background: Oral sGC stimulators are novel treatments for heart failure (HF). Since individual studies are limited to confirm the efficacy and safety of sGC stimulators in patients with HF, we provide a meta-analysis based on published clinical randomized controlled trials. Methods: Embase, PubMed, Cochrane and Medline were applied to search for randomized controlled trials (published before March 29, 2020 without language restrictions) by comparing oral sGC stimulators to placebos. Main endpoints were efficacy outcomes, including all-cause mortality, incidence of cardiovascular-events related death or hospitalization, alterations of EQ-5D index, and N-terminal (NT)-pro hormone BNP(NT-proBNP); and safety outcomes included incidence of serious adverse events (SAEs), symptomatic hypotension and syncope. Results: Six trials were enrolled (N=6255 participants), sGC stimulators yielded a lower incidence of cardiovascular-events related death or hospitalization (OR=0.88, 95% CI=0.79 to 0.98), an improvement in EQ-5D scores (SMD=0.44, 95% CI=0.24 to 0.63), and a lower relative risk of SAEs (OR=0.90, 95% CI=0.81 to 1.00) compared with placebos. Furthermore, NT-proBNP was decreased by riociguat (SMD=-0.79, 95% CI=-1.10 to -0.49), but not by vericiguat (SMD=0.04, 95% CI=-0.18 to 0.25). There was no significant difference in all-cause mortality (OR=0.95, 95% CI=0.83 to 1.09), incidence of symptomatic hypotension (OR=1.15, 95% CI=0.95 to 1.40) and syncope (OR=1.15, 95% CI=0.87 to 1.53) between sGC stimulators and placebos. Conclusion: Oral sGC stimulators may be beneficial for HF with a good tolerance, further studies are also needed to establish the optimal approach in clinical practice.