作者：余浩瑗，王东英，冯旸，边云飞

单位：

1.030000山西省太原市，山西医科大学　2.030000山西省太原市，山西医科大学第二医院心血管内科

Units：

1.Shanxi Medical University, Taiyuan 030000, China2.Department of Cardiovascular, Second Hospital of Shanxi Medical University, Taiyuan 030000, China

关键词：

心力衰竭；血管紧张素受体脑啡肽酶抑制剂；omecamtiv mecarbil；钠-葡萄糖协同转运蛋白2抑制剂；可溶性鸟苷酸环化酶刺激剂；网状Meta分析

Keywords：

Heart failure; ARNI; omecamtiv mecarbil; SGLT2i; sGCs; Network Meta-analysis

CLC：

R 541.62

DOI：

10.12114/j.issn.1008-5971.2023.00.127

Funds：

国家自然科学基金资助项目（82070472）

摘要：

目的　采用网状Meta分析方法比较血管紧张素受体脑啡肽酶抑制剂（ARNI）、omecamtiv mecarbil、钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）或可溶性鸟苷酸环化酶刺激剂（sGCs）治疗慢性心力衰竭（CHF）的效果。方法　计算机检索PubMed、Embase、Cochrane Library、中国知网、万方数据知识服务平台、维普网中ARNI、SGLT2i、sGCs或omecamtiv mecarbil治疗CHF的随机对照试验，检索时限为建库至2020-10-29。主要结局指标是心血管死亡和因心力衰竭（HF）住院复合事件发生率，次要结局指标是因HF再住院率、心血管死亡率、全因死亡率、堪萨斯城心肌病问卷评分（KCCQ）评分及不良反应发生率。使用贝叶斯统计方法进行网状Meta分析，使用ReviewManager 5.3、Stata 17.0软件进行统计学处理。采用累积排序概率曲线下面积（SUCRA）比较四种新型抗HF药物治疗CHF的效果。结果　最终纳入21篇文献，涉及45 285例CHF患者。网状Meta分析结果显示：（1）行ARNI+常规抗HF治疗、sGCs+常规抗HF治疗、SGLT2i+常规抗HF治疗者心血管死亡和因HF住院复合事件发生率低于行常规抗HF治疗者，行omecamtiv mecarbil+常规抗HF治疗者心血管死亡和因HF住院复合事件发生率高于行ARNI+常规抗HF治疗、SGLT2i+常规抗HF治疗者（P＜0.05）。根据SUCRA排序依次为SGLT2i+常规抗HF治疗（95.4%）、ARNI+常规抗HF治疗（90.8%）、sGCs+常规抗HF治疗（69.1%）、omecamtiv mecarbil+常规抗HF治疗（69.5%）、常规抗HF治疗（95.0%）。（2）行ARNI+常规抗HF治疗、SGLT2i+常规抗HF治疗者因HF再住院率低于行常规抗HF治疗者，行omecamtiv mecarbil+常规抗HF治疗者因HF再住院率高于行ARNI+常规抗HF治疗者，行SGLT2i+常规抗HF治疗者因HF再住院率低于行ARNI+常规抗HF治疗、omecamtiv mecarbil+常规抗HF治疗、sGCs+常规抗HF治疗者（P＜0.05）。根据SUCRA排序依次为SGLT2i+常规抗HF治疗（99.5%）、ARNI+常规抗HF治疗（97.4%）、sGCs+常规抗HF治疗（81.2%）、omecamtiv mecarbil+常规抗HF治疗（66.1%）、常规抗HF治疗（80.3%）。（3）行ARNI+常规抗HF治疗、SGLT2i+常规抗HF治疗者心血管死亡率低于行常规抗HF治疗者（P＜0.05）。根据SUCRA排序依次为ARNI+常规抗HF治疗（71.8%）、SGLT2i+常规抗HF治疗（58.9%）、sGCs+常规抗HF治疗（55.0%）、常规抗HF治疗（55.5%）、omecamtiv mecarbil+常规抗HF治疗（53.9%）。（4）行ARNI+常规抗HF治疗者全因死亡率低于行常规抗HF治疗者（P＜0.05）。根据SUCRA排序依次为ARNI+常规抗HF治疗（43.0%）、SGLT2i+常规抗HF治疗（37.9%）、常规抗HF治疗（22.8%）、omecamtiv mecarbil+常规抗HF治疗（21.1%）、sGCs+常规抗HF治疗（26.7%）。（5）行SGLT2i+常规抗HF治疗者KCCQ评分高于行常规抗HF治疗、omecamtiv mecarbil+常规抗HF治疗者（P＜0.05）。根据SUCRA排序依次为SGLT2i+常规抗HF治疗（96.0%）、ARNI+常规抗HF治疗（81.5%）、常规抗HF治疗（69.2%）、omecamtiv mecarbil+常规抗HF治疗（71.8%）。因部分研究未记录不良反应，且不良反应的标准、分类和评估方法可能存在差异，故暂不做进一步分析。结论　ARNI和SGLT2i治疗CHF的效果优于sGCs和omecamtiv mecarbil，其中ARNI在降低CHF患者心血管死亡率和全因死亡率方面效果可能最佳，SGLT2i在降低心血管死亡和因HF住院复合事件发生率、因HF再住院率和改善患者活动耐量、生活质量方面效果可能最佳。

Abstract：

Objective To compare the efficacy of angiotensin receptor neprilysin inhibitor (ARNI) , omecamtivmecarbil, sodium-glucose cotransporter 2 inhibitor (SGLT2i) or soluble guanylate cyclase stimulators (sGCs) in the treatment ofchronic heart failure (CHF) using network meta-analysis. Methods The randomized controlled trials of ARNI, SGLT2i, sGCsor omecamtiv mecarbil in the treatment of CHF were searched in PubMed, Embase, Cochrane Library, CNKI, Wanfang Data andVIP. The search deadline was from the establishment of the database to 2020-10-29. The primary outcome indicator was theindicine of complex events of cardiovascular death and hospitalization due to heart failure (HF) . The secondary outcome indicatorswere rehospitalization due to HF, cardiovascular mortality, all-cause mortality, Kansas City Cardiomyopathy Questionnaire(KCCQ) score and incidence of adverse reactions. Bayesian statistical method was used for network meta-analysis, and ReviewManager 5.3 and Stata 17.0 software were used for statistical analysis. The surface under the cumulative ranking curve (SUCRA)was used to compare the effects of four new anti-HF drugs on CHF. Results Finally, 21 articles were included, involving45 285 CHF patients. The results of network meta-analysis showed that: (1) The incidence of complex events of cardiovasculardeath and hospitalization due to HF in patients treated with ARNI+conventional anti-HF treatment, sGCs+conventional anti-HFtreatment, SGLT2i+conventional anti-HF treatment was lower than that in patients treated with conventional anti-HF treatment,and the incidence of complex events of cardiovascular death and hospitalization due to HF in patients treated with omecamtivmecarbil+conventional anti-HF treatment was higher than that in patients treated with ARNI+conventional anti-HF treatmentand SGLT2i+conventional anti-HF treatment (P < 0.05) . According to SUCRA, the order was SGLT2i+conventional anti-HFtreatment (95.4%) , ARNI+conventional anti-HF treatment (90.8%) , omecamtiv mecarbil+conventional anti-HF treatment(69.5%) , sGCs+conventional anti-HF treatment (69.1%) , conventional anti-HF treatment (95.0%) . (2) The rehospitalizationrate due to HF in patients treated with ARNI+conventional anti-HF treatment and SGLT2i+conventional anti-HF treatment waslower than that in patients treated with conventional anti-HF treatment, and the rehospitalization rate due to HF in patients treatedwith omecamtiv mecarbil+conventional anti-HF treatment was higher than that in patients treated with ARNI+conventionalanti-HF treatment, and rehospitalization rate due to HF in patients treated with SGLT2i+conventional anti-HF treatment waslower than that in patients treated with ARNI+conventional anti-HF treatment, omecamtiv mecarbil+conventional anti-HFtreatment, sGCs+conventional anti-HF treatment (P < 0.05) . According to SUCRA, the order was SGLT2i+conventional anti-HFtreatment (99.5%) , ARNI+conventional anti-HF treatment (97.4%) , sGCs+conventional anti-HF treatment (81.2%) , omecamtivmecarbil+conventional anti-HF treatment (66.1%) , conventional anti-HF treatment (80.3%) . (3) The cardiovascular mortalityof patients treated with ARNI+conventional anti-HF treatment and SGLT2i+conventional anti-HF treatment was lower than thatof patients treated with conventional anti-HF treatment (P < 0.05) . According to SUCRA, the order was ARNI+conventionalanti-HF treatment (71.8%) , SGLT2i+conventional anti-HF treatment (58.9%) , sGCs+conventional anti-HF treatment(55.0%) , conventional anti-HF treatment (55.5%) , omecamtiv mecarbil+conventional anti-HF treatment (53.9%) . (4) Theall-cause mortality of patients treated with ARNI+conventional anti-HF treatment was lower than that of patients treated withconventional anti-HF treatment (P < 0.05) . According to SUCRA, the order was ARNI+conventional anti-HF treatment (43.0%) ,SGLT2i+conventional anti-HF treatment (37.9%) , conventional anti-HF treatment (22.8%) , omecamtiv mecarbil+conventionalanti-HF treatment (21.1%) , sGCs+conventional anti-HF treatment (26.7%) . (5) The KCCQ score of SGLT2i+conventionalanti-HF treatment was higher than that of conventional anti-HF treatment and omecamtiv mecarbil+conventional anti-HFtreatment (P < 0.05) . According to SUCRA, the order was SGLT2i+conventional anti-HF treatment (96.0%) , ARNI+conventionalanti-HF treatment (81.5%) , conventional anti-HF treatment (69.2%) , omecamtiv mecarbil+conventional anti-HF treatment(71.8%) . Because some studies did not record adverse reactions, and there may be differences in the criteria, classification andevaluation methods of adverse reactions, no further analysis was performed. Conclusion The effects of ARNI and SGLT2i in thetreatment of CHF are better than those of sGCs and omecamtiv mecarbil. Among them, ARNI may have the best effect in reducingcardiovascular mortality and all-cause mortality in CHF patients, and SGLT2i may have the best effect in reducing the incidenceof complex events of cardiovascular death and hospitalization due to HF, the rate of rehospitalization due to HF, and improvingactivity tolerance and quality of life of patients.

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