Objective  Heart failure with preserved ejection fraction (HFpEF) are more common in patients with heart failure in China. Currently, there is no definitive drug recommendations for the effective treatment of patients with HFpEF in clinical guidelines. It is necessary to study the efficacy and safety of novel oral soluble guanylate cyclase (sGC) stimulators. The aim of this study was to investigate the efficacy and safety of sGC stimulators in patients with HFpEF.

Methods  We searched the published randomized controlled trials (RCTs) comparing sGC stimulators with placebo in patients with HFpEF from the database of PubMed, Embase and the Cochrane library up to October, 2022. A total of 1 756 individuals with HFpEF were included in this Meta-analysis.

Results  Compared with placebo, sGC stimulators improved EuroQol Group 5-Dmensional Self-report Questionnaire (EQ-5D) index score (MD=0.07, 95%CI=0.06 to 0.08, P<0.001), the Kansas City Cardiomyopathy Questionnaire physical limitation score (KCCQ-PLS) (MD=9.99, 95%CI=8.86 to 11.12, P<0.001) and 6-minute walk distance test (6MWT) score (MD=7.11, 95%CI=5.48 to 8.74, P<0.001). No effects on the all-cause mortality (RR=1.29, 95%CI=0.67 to 2.50, P=0.45) and the risk of Major Adverse Cardiovascular Events (MACEs) (RR=1.16, 95%CI=0.80 to 1.67, P=0.43) were observed. Furthermore, sGC stimulators failed showing beneficial effects on E/e′ ratio (MD=-0.94, 95%CI=-2.12 to 0.24, P=0.12), E/A (MD=-0.07, 95%CI=-0.14 to 0.28, P=0.52), left atrial volume (MD=-0.35, 95%CI=-1.75 to 2.45, P=0.75), left ventricular end-systolic volume (SMD=-3.57, 95%CI=-22.36 to 29.5, P=0.79), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (SMD=-0.97, 95%CI=-2.04 to 0.10, P=0.08).

Conclusion  sGC stimulators significantly improve exercise tolerance and quality of life without confirmed beneficial effect on all-cause mortality and the diastolic functional parameters determined by echocardiography.

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