选择性心肌肌球蛋白激动剂Omecamtiv mecarbil治疗心力衰竭有效性和安全性的meta分析

Efficacy and Safety of Selective Cardiac Myosin Activators Omecamtiv Mecarbil in the Treatment of Heart Failure: A Meta-analysis

关键词:  心力衰竭  选择性心肌肌球蛋白激动剂  meta分析  随机对照试验

Key words:  heart failure  selective cardiac myosin activators  meta-analysis  randomized controlled trial

摘要:

目的 系统评价选择性心肌肌球蛋白激动剂Omecamtiv mecarbil(OM)治疗心力衰竭(heart failure，HF)的有效性与安全性。方法 计算机检索PubMed、EMbase、The Cochrane Library、Web of Science、CNKI、Science Direct、Wanfang Data和CBM等数据库，搜集选择性心肌肌球蛋白激动剂治疗HF有效性和安全性相关的随机对照研究(randomized controlled trial，RCT)，检索时限为建库至2021年7月，由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后，采用RevMan 5.3软件进行meta分析。结果 共纳入了6个RCT，包括9429例患者，试验组4763例，对照组4666例；meta分析结果显示，与对照组相比，选择性心肌肌球蛋白激动剂未降低HF患者主要终点事件：心血管(cardiovascular，CV)死亡/因HF住院(HF hospitalization，HHF)复合事件[RR=1.19，95%CI(0.67，2.12)，P=0.54]、HHF率[RR=0.96，95%CI(0.90，1.03)，P=0.29]、CV死亡率[RR=1.01，95％CI(0.92，1.10)，P=0.88]和全因死亡率[RR=1.00，95%CI(0.93，1.07)，P=0.90]。但选择性心肌肌球蛋白激动剂OM显著改善了HF患者的堪萨斯城HF调查表(the Kansas City Cardiomyopathy Questionnaire，KCCQ)临床评分[MD=2.50，95％CI(2.47，2.53)，P<0.00001]、左室射血分数(left ventricular ejection fraction，LVEF%)[MD=7.20，95%CI(2.51，11.89)，P=0.003]、左室舒张末期容积(left ventricular end diastolic volume，LVEDV)[MD=-0.35，95%CI(-0.61，-0.08)，P=0.009]、左室收缩末期容积(left ventricular end systolic volume，LVESV)[MD=-2.78，95%CI(-3.70，-1.87)，P<0.00001]、每搏输出量(stroke volume,SV)[MD=8.80，95%CI(1.37，16.23)，P=0.02]等心功能参数；除此之外，2组严重不良事件(serious adverse events，SAE)发生率相似[RR=0.97，95%CI(0.94，1.01)，P=0.16]，2组急性肾损伤、症状性低血压、呼吸困难等不良事件的发生率也无差异。结论 现有证据表明，选择性心肌肌球蛋白激动剂OM可以明显改善KCCQ临床评分、LVEF%、LVEDV、LVESV及每搏输出量等心功能参数，而且不增加不良事件风险，但对HF患者CV死亡和HHF复合事件、HHF率，CV死亡率和全因死亡率方面无明显益处。

Abstract:

OBJECTIVE To systematically evaluate the efficacy and safety of selective novel cardiac myosin activators Omecamtiv mecarbil(OM) in the treatment of heart failure(HF). METHODS PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Science Direct, Wanfang Data and CBM databases were electronically searched to collect randomized controlled trials(RCT) about the efficacy and safety of selective cardiac myosin activators in the treatment of HF from inception to July 2021. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 6 RCT including 9 429 HF patients(4 763 in the experimental group, and 4 666 in the control group) were included. The results of meta-analysis showed that compared with control group, selective cardiac myosin activators did not reduce primary endpoints of HF patients[a composite of cardiovascular(CV) mortality and HF hospitalization(HHF)] [RR=1.19, 95% CI (0.67, 2.12), P=0.54], HHF rate[RR=0.96, 95%CI(0.90, 1.03), P=0.29], CV mortality[RR=1.01, 95%CI(0.92, 1.10), P=0.88] and all-cause mortality[RR=1.00, 95%CI(0.93, 1.07), P=0.90]. However, cardiac myosin activator OM significantly improved the Kansas City Cardiomyopathy Questionnaire(KCCQ) clinical scores[MD=2.50, 95% CI(2.47, 2.53), P<0.000 01], left ventricular ejection fraction (LVEF%)[MD=7.20, 95%CI(2.51, 11.89), P=0.003], left ventricular end diastolic volume(LVEDV)[MD=-0.35, 95% CI (-0.61, -0.08), P=0.009], left ventricular end systolic volume(LVESV)[MD=-2.78, 95% CI(-3.70, -1.87), P<0.000 01] and stroke volume(SV)[MD=8.80, 95% CI(1.37, 16.23), P=0.02] and other cardiac function parameters. Besides, the incidence of serious adverse events(SAE) was similar in two groups[RR=0.97, 95% CI(0.94, 1.01), P=0.16], and there were no significant differences between two groups in the incidence of acute kidney injury, symptomatic hypotension and dyspnea. CONCLUSION Current evidence indicates that selective cardiac myosin activators OM can significantly improve heart function parameters of KCCQ clinical scores, LVEF%, LVEDV, LVESV and stroke volume, without increasing the risk of adverse events, but have no significant benefit in terms of the composite of CV mortality and HHF, HHF rate, CV mortality and all-cause mortality in HF patients.