沙库巴曲缬沙坦治疗非射血分数降低心力衰竭疗效和安全性的Meta分析(1)
摘 要 目的：系统评价沙库巴曲缬沙坦治疗非射血分数降低心力衰竭(non-HFrEF)的有效性和安全性，为临床治疗提供循证参考。方法：计算机检索Cochrane图书馆、PubMed、Embase、中国知网、维普和万方数据等，检索时限均为建库起至2020年2月29日。收集沙库巴曲缬沙坦(试验组)对比肾素-血管紧张素转化酶抑制剂/血管紧张素Ⅱ受体拮抗药(对照组)等常规药物用于治疗non-HFrEF的随机对照试验(RCT)。筛选文献、提取资料后，采用Cochrane偏倚风险评估工具5.3.0对纳入文献质量进行评价，采用Stata 14.0软件进行Meta分析，并行发表偏倚和敏感性分析。结果：共纳入6项RCT，共计5 502例患者。Meta分析结果显示，试验组患者心力衰竭再住院率[RR=0.84，95%CI(0.77，0.91)，P<0.001]、血肌酐升高发生率[RR=0.78，95%CI(0.67，0.91)，P=0.001]均显著低于对照组，纽约心脏病协会心功能分级改善率[RR=1.25，95%CI(1.10，1.43)，P=0.001]、低血压发生率[RR=1.43，95%CI(1.24，1.65)，P<0.001]均显著高于对照组;两组患者心血管相关死亡率[RR=0.94，95%CI(0.79，1.12)，P=0.481]、全因死亡率[RR=0.95，95%CI(0.83，1.08)，P=0.417]、治疗后氨基末端脑钠肽前体水平[WMD=-301.16，95%CI(-602.77，0.44)，P=0.050]、左心室射血分数水平[WMD=1.49，95%CI(-1.33，4.32)，P=0.300]、高钾血症发生率[RR=0.88，95%CI(0.77，1.01)，P=0.070]比较，差异均无统计学意义。发表偏倚和敏感性分析结果均显示，存在发表偏倚的可能性较大，且部分指标结果不稳定。结论：沙库巴曲缬沙坦可能会有效降低non-HFrEF患者的心力衰竭再住院率及血肌酐升高发生风险，改善其心功能，但低血压发生风险较高。上述结果需谨慎解读。
关键词 沙库巴曲缬沙坦;非射血分数降低心力衰竭;有效性;安全性;Meta分析
中圖分类号 R541 文献标志码 A 文章编号 1001-0408(2020)18-2263-06
DOI 10.6039/j.issn.1001-0408.2020.18.16
ABSTRACT OBJECTIVE： To systematically evaluate the efficacy and safety of sacubitril-valsartan in the treatment of heart failure without reduced ejection fraction (non-HFrEF) patients， and to provide evidence-based reference for its clinical treatment. METHODS： Retrieved from Cochrane Library， PubMed， Embase， CNKI， VIP and Wanfang data， during the inception to Feb. 29th， 2020， randomized controlled trials (RCTs) about sacubitril-valsartan (trial group) versus routine medicine as renin-angio- tensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists (control group) in the treatment of non-HFrEF were collected. After literature screening and data extraction， the quality of included literatures were evaluated with Cochrane bias risk evaluation tool 5.3.0. Meta-analysis was conducted with Stata 14.0 software， and the publication bias analysis and sensitivity analysis were performed. RESULTS： Totally 6 RCTs were included， involving 5 502 patients. Results of Meta-analysis showed that the HF re-hospitalization rate [RR=0.84， 95%CI (0.77， 0.91)， P<0.001] and the serum creatinine elevation rate [RR=0.78， 95%CI (0.67， 0.91)， P=0.001] in trial group were significantly lower than control group. NYHA classification improvement rate [RR=1.25， 95%CI (1.10， 1.43)， P=0.001] and the hypotension rate [RR=1.43， 95%CI (1.24， 1.65)， P<0.001] were significantly higher than control group. There was no statistical significance in the cardiovascular mortality [RR=0.94， 95%CI (0.79， 1.12)， P=0.481]， all-cause mortality [RR=0.95， 95%CI (0.83， 1.08)， P=0.417]， the levels of NT-proBNP [WMD=-301.16， 95%CI (-602.77， 0.44)， P=0.050] and LVEF [WMD=1.49， 95%CI (-1.33， 4.32)， P=0.300] after treatment， and the hyperkalaemia rate [RR=0.88， 95%CI (0.77， 1.01)， P=0.070] between 2 groups. The results of publication bias analysis and sensitivity analysis showed there was a high possibility of publication bias， and the results of several indexes were not stable. CONCLUSIONS： Sacubitril-valsartan may effectively reduce HF re-hospitalization rate and the risk of elevated serum creatinine in non-HFrEF patients， improve the heart function but the risk of hypoten- sion is high. The results should be interpreted carefully., 百拇医药(熊波 钱俊 容顺康 姚沅清 黄晶)
关键词 沙库巴曲缬沙坦;非射血分数降低心力衰竭;有效性;安全性;Meta分析
中圖分类号 R541 文献标志码 A 文章编号 1001-0408(2020)18-2263-06
DOI 10.6039/j.issn.1001-0408.2020.18.16
ABSTRACT OBJECTIVE： To systematically evaluate the efficacy and safety of sacubitril-valsartan in the treatment of heart failure without reduced ejection fraction (non-HFrEF) patients， and to provide evidence-based reference for its clinical treatment. METHODS： Retrieved from Cochrane Library， PubMed， Embase， CNKI， VIP and Wanfang data， during the inception to Feb. 29th， 2020， randomized controlled trials (RCTs) about sacubitril-valsartan (trial group) versus routine medicine as renin-angio- tensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists (control group) in the treatment of non-HFrEF were collected. After literature screening and data extraction， the quality of included literatures were evaluated with Cochrane bias risk evaluation tool 5.3.0. Meta-analysis was conducted with Stata 14.0 software， and the publication bias analysis and sensitivity analysis were performed. RESULTS： Totally 6 RCTs were included， involving 5 502 patients. Results of Meta-analysis showed that the HF re-hospitalization rate [RR=0.84， 95%CI (0.77， 0.91)， P<0.001] and the serum creatinine elevation rate [RR=0.78， 95%CI (0.67， 0.91)， P=0.001] in trial group were significantly lower than control group. NYHA classification improvement rate [RR=1.25， 95%CI (1.10， 1.43)， P=0.001] and the hypotension rate [RR=1.43， 95%CI (1.24， 1.65)， P<0.001] were significantly higher than control group. There was no statistical significance in the cardiovascular mortality [RR=0.94， 95%CI (0.79， 1.12)， P=0.481]， all-cause mortality [RR=0.95， 95%CI (0.83， 1.08)， P=0.417]， the levels of NT-proBNP [WMD=-301.16， 95%CI (-602.77， 0.44)， P=0.050] and LVEF [WMD=1.49， 95%CI (-1.33， 4.32)， P=0.300] after treatment， and the hyperkalaemia rate [RR=0.88， 95%CI (0.77， 1.01)， P=0.070] between 2 groups. The results of publication bias analysis and sensitivity analysis showed there was a high possibility of publication bias， and the results of several indexes were not stable. CONCLUSIONS： Sacubitril-valsartan may effectively reduce HF re-hospitalization rate and the risk of elevated serum creatinine in non-HFrEF patients， improve the heart function but the risk of hypoten- sion is high. The results should be interpreted carefully., 百拇医药(熊波 钱俊 容顺康 姚沅清 黄晶)