Soluble guanylate cyclase (sGC) stimulators in heart failure with preserved ejection fraction: a systematic review and meta-analysis

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 1600 HFpEF patients. Comprehensively, the combined risk ratio (RR) for mortality was not significant(RR(95% CI) = 1.44 (0.71-2.91), p = 0.31). Furthermore, there were no statistically significant differences in the Kansas City Cardiomyopathy Questionnaire (KCCQ) results, including the Clinical Summary Score(CSS) (WMD (95% CI) =0.32( -7.38-8.02), p = 0.94) and the Overall Summary Score(OSS) (WMD (95% CI) = -0.87( -8.87-7.14), P = 0.83). Similarly, there was no significant improvement in the 6-minute walk distance(6MWD) (WMD(95% CI) = -6.22(-18.56-6.12), p = 0.32). Additionally, 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). Conclusions 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.