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Updated: Jul 10, 2025

Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
SOLUBLE GUANYLATE CYCLASE STIMULATORS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION: A SYSTEMATIC REVIEW AND
Yang Zhao1, Bin Zang1, Qian Wang2
1Department of Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
Insights
Soluble guanylate cyclase (sGC) stimulators did not improve mortality or quality of life in heart failure with preserved ejection fraction (HFpEF) patients. These drugs increased adverse events, warranting cautious use in HFpEF treatment.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Heart failure with preserved ejection fraction (HFpEF) presents a significant therapeutic challenge.
- Soluble guanylate cyclase (sGC) stimulators are a class of drugs investigated for HFpEF treatment.
- Evidence regarding their efficacy and safety in HFpEF remains under evaluation.
Conclusions:
- Oral sGC stimulators do not offer significant benefits for mortality, functional capacity, or quality of life in HFpEF.
- sGC stimulators are associated with a higher incidence of drug-related adverse events.
- Careful consideration is advised when using sGC stimulators in HFpEF patients due to the observed risk-benefit profile.
Abstract:
Aims: We conducted a systemic review and meta-analysis to evaluate the therapeutic efficacy and safety of soluble guanylate cyclase (sGC) stimulators in patients with heart failure with preserved ejection fraction (HFpEF). Methods : We systematically searched PubMed, Embase, and Cochrane Library databases for original randomized controlled trials comparing sGC stimulators with placebo in HFpEF patients. A random-effects model was applied to evaluate the mortality, quality of life, and drug-related adverse events. This meta-analysis is registered in PROSPERO under the number CRD42023457382. Results : We included five studies involving 1,600 HFpEF patients. Comprehensively, the combined risk ratio (RR) for mortality was not significant (RR [95% CI] = 1.44 [0.71 to 2.91], P = 0.31). Furthermore, there were no statistically significant differences in the Kansas City Cardiomyopathy Questionnaire results, including the clinical summary score (weighted mean difference [WMD] [95% CI] =0.32 [-7.38 to 8.02], P = 0.94) and the overall summary score (WMD [95% CI] = -0.87 [-8.87 to 7.14], P = 0.83). Similarly, there was no significant improvement in the 6-minute walk distance (WMD [95% CI] = -6.22 [-18.56 to 6.12], P = 0.32). In addition, drug-related adverse events were more common in patients treated with sGC stimulators (RR [95% CI] = 1.63 [1.25-2.14], P < 0.05). Conclusion : Oral sGC stimulators do not significantly improve mortality outcomes, functional capacity, and quality of life in HFpEF patients but are associated with increased drug-related adverse events. Therefore, we should consider using sGC stimulators in HFpEF patients carefully.
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Pathophysiology of Heart Failure

