BACKGROUND Soluble guanylate cyclase (sGC) stimulators are a novel class of medications with emerging role in heart failure (HF). The aim of this study is to evaluate the efficacy and safety of oral sGC stimulators in patients with HF with reduced and preserved ejection fraction (HFrEF and HFpEF) by pooling data from all available randomized control trials (RCT). METHODS A comprehensive search of electronic databases from 2000-2020 was performed. Seven RCTs, three HFrEF and four HFpEF studies, were identified. The follow-up duration ranged from 1 month to a median of 10.8 months. A random-effects meta-analysis was conducted to summarize the studies. RESULTS The study population included 7190 patients: 5707 HFrEF and 1483 HFpEF patients. In HFrEF, oral sGC stimulators reduced the composite incidence of HF hospitalization and cardiovascular death (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97; I2 = 0%), primarily driven by lower HF hospitalization (HR 0.88, 95% CI 0.78-0.99; I2 = 0%). There was no significant reduction in all-cause death in HFrEF (HR 0.95, 95% CI 0.83-1.09; I2 = 0%). In HFpEF, there were no improvements in Kansas City Cardiomyopathy Questionnaire clinical summary scores (mean difference 0.81, 95% CI -2.16-3.77; I2 = 72%) or 6-minute walk distance (mean difference 3.34 meters, 95% CI -7.86-14.54; I2 = 28%). There was no difference in all-cause mortality in HFpEF (HR 1.94, 95% CI 0.92-4.09; I2 = 0%). Overall, oral sGC stimulators had low medication-related serious adverse events. CONCLUSION Oral sGC stimulators are well tolerated in HF and reduce the incidence of HF hospitalization but not cardiovascular death among patients with HFrEF. However, there are no apparent benefits in HFpEF.

中文翻译：

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口服可溶性鸟苷酸环化酶刺激剂对心力衰竭的影响：随机对照试验的系统评价和荟萃分析。

背景可溶性鸟苷酸环化酶（sGC）刺激剂是一类新型药物，在心力衰竭（HF）中发挥着新的作用。本研究的目的是通过汇集所有可用随机对照试验 (RCT) 的数据，评估口服 sGC 刺激剂对射血分数降低和保留的 HF 患者（HFrEF 和 HFpEF）的疗效和安全性。方法 对 2000-2020 年的电子数据库进行了全面搜索。确定了七项 RCT、三项 HFrEF 和四项 HFpEF 研究。随访时间从 1 个月到中位数 10.8 个月不等。进行了随机效应荟萃分析来总结研究。结果 研究人群包括 7190 名患者：5707 名 HFrEF 患者和 1483 名 HFpEF 患者。在 HFrEF 中，口服 sGC 刺激剂降低了 HF 住院和心血管死亡的复合发生率（风险比 [HR] 0.87，95% 置信区间 [CI] 0.78-0.97；I2 = 0%），主要是由于较低的 HF 住院率（HR 0.88，95%） CI 0.78-0.99；I2 = 0%)。HFrEF 的全因死亡没有显着降低（HR 0.95，95% CI 0.83-1.09；I2 = 0%）。在 HFpEF 中，堪萨斯城心肌病问卷临床总结评分（平均差 0.81，95% CI -2.16-3.77；I2 = 72%）或 6 分钟步行距离（平均差 3.34 米，95% CI -7.86）没有改善-14.54；I2 = 28%）。HFpEF 的全因死亡率没有差异（HR 1.94，95% CI 0.92-4.09；I2 = 0%）。总体而言，口服 sGC 刺激剂与药物相关的严重不良事件较少。结论 口服 sGC 刺激剂在 HF 中具有良好的耐受性，可降低 HFrEF 患者的 HF 住院发生率，但不会降低心血管死亡的发生率。然而，HFpEF 没有明显的好处。