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。
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 9429 HF patients(4763 in the experimental group,and 4666 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<0.00001],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<0.00001]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.
作者
贾晓艳
安晋阳
彭可玲
王华
刘永铭
JIA Xiaoyan;AN Jinyang;PENG Keling;WANG Hua;LIU Yongming(The First School of Clinical Medicine,Lanzhou University,Lanzhou 730000,China;Department of Geriatric Cardiology,The First Hospital of Lanzhou University,Gansu Provincial Clinical Research Center for Geriatric Medicine,Lanzhou 730000,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2022年第23期3127-3137,共11页
Chinese Journal of Modern Applied Pharmacy
基金
甘肃省重点研发计划(20YF8FA079)。
作者简介
贾晓艳,女,硕士生,E-mail:zzdxjiaxiaoyao@163.com;通信作者:刘永铭,男,硕士,主任医师,E-mail:cardtonm@263.net。
