可溶性鸟苷酸环化酶激动剂治疗心力衰竭疗效和安全性的网状Meta分析

Efficacy and safety of soluble guanylate cyclase stimulators in treatment of heart failure:a network meta-analysis

目的采用网状Meta分析比较新型口服可溶性鸟苷酸环化酶(sGC)激动剂治疗心力衰竭(心衰)的疗效和安全性。方法计算机检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方和中国生物医学文献数据库(CBM)等,搜集sGC激动剂治疗心衰相关的随机对照研究(RCT),检索时限为建库至2021年5月。按照Cochrane系统评价手册对纳入研究的方法学进行质量评价,采用RevMan 5.3和Stata 15.1软件进行数据分析。结果共纳入了8项RCT,总计7223例心衰患者,涉及3种sGC激动剂共12个干预措施。网状Meta分析结果显示,与安慰剂相比,维立西呱10 mg·d^(-1)可以降低因心衰住院率(RR=0.92,95%CI:0.84~1.00,P<0.05),其他各干预措施之间相比无显著差异(P>0.05)。与安慰剂相比,3种sGC激动剂在严重不良事件、急性肾损伤和症状性低血压发生率方面均无显著差异(P>0.05)。累计排序概率曲线下面积(SUCRA)排序结果显示,在降低心血管死亡和因心衰住院复合事件率方面,维立西呱10 mg·d^(-1)疗效最佳,而利奥西呱2 mg tid在降低全因死亡率方面最优。结论现有证据表明,在sGC激动剂中,维立西呱10 mg·d^(-1)是治疗心衰的最佳方案,各s GC激动剂安全性均较好。受纳入研究质量的限制,上述结论尚需开展更多高质量研究予以验证。

AIM To assess the clinical efficacy and safety of novel oral soluble guanylate cyclase(sGC)stimulators in the treatment of heart failure(HF)by using a network meta-analysis.METHODS PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang and CBM databases were electronically searched to collect randomized controlled trials(RCTs)related to sGC stimulators in the treatment of HF from inception to May 2021.The methodological quality assessment of included studies was evaluated by the Cochrane handbook,and network meta-analysis was performed by RevMan 5.3 and Stata 15.1 software.RESULTS Eight RCTs were included,with a total of 7223 HF patients,involving 12 interventions.The results of network meta-analysis showed that compared with placebo,vericiguat 10 mg·d^(-1)reduced the HF hospitalization rate(RR=0.92,95%CI:0.84 to 1.00,P<0.05),but there was no significant difference among other interventions with various sGC stimulators on the composite event rate of cardiovascular mortality or all-cause mortality in HF patients(P>0.05).Compared with placebo,the three sGC agonists had no significant difference in the incidence of total severe adverse events,acute renal injury and symptomatic hypotension(P>0.05).The area under the cumulative ranking(SUCRA)sorting results showed vericiguat 10 mg·d^(-1)was the most effective in reducing composite event rate of cardiovascular death and HF hospitalization,and riociguat 2 mg tid was the best in reducing all-cause mortality.CONCLUSION The current evidence shows that vericiguat 10 mg·d^(-1)is the most effective sGC stimulator regimen in the treatment of HF,and the safety of each sGC stimulators is better.Due to the limitation of the quality and quantity of the included studies,the above conclusions also need to be verified by more high-quality studies.