Section of Cardiovascular Medicine (J.-R.D.C., R.R., N.R.D., T.A.), Yale University School of Medicine, New Haven, CT.
Division of Cardiology, School of Medicine, University of Colorado, Aurora (L.A.A.).
Circ Heart Fail. 2021 Feb;14(2):e007759. doi: 10.1161/CIRCHEARTFAILURE.120.007759. Epub 2021 Feb 3.
A growing population of patients with end-stage heart failure (HF) with reduced ejection fraction has limited treatment options to improve their quality and quantity of life. Although positive inotropes have failed to show survival benefit, these agents may enhance patient-reported health status, that is, symptoms, functional status, and health-related quality of life. We sought to review the available clinical trial data on positive inotrope use in patients with end-stage HF and to summarize evidence supporting the use of these agents to improve health status of patients with end-stage HF.
A literature review of randomized controlled trials examining the use of positive inotropy in HF with reduced ejection fraction was conducted. We searched MEDLINE, SCOPUS, and Web of Science between January 1980 to December 2018 for randomized controlled trials that used as their main outcome measures the effects of inotrope therapy on (1) morbidity/mortality, (2) symptoms, (3) functional status, or (4) health-related quality of life. Inotropes of interest included adrenergic agents, phosphodiesterase inhibitors, calcium sensitizers, myosin activators, and SERCA2a (sarcoplasmic reticulum Ca-ATPase) modulators.
Twenty-two out of 26 inotrope randomized controlled trials measured the effect of inotropes on at least one patient-reported health status domain. Among the 22 studies with patient-related health status outcomes, 11 (50%) gauged symptom response, 15 (68%) reported functional capacity changes, and 12 (54%) reported health-related quality of life measures. Fourteen (64%) of these trials noted positive outcomes in at least one health status domain measured; 11 (79%) of these positive studies used agents that worked through phosphodiesterase inhibition.
There has been a lack of standardization surrounding measurement of patient-centered outcomes in studies of inotropes for end-stage HF with reduced ejection fraction. The degree to which positive inotropes can improve patient-reported health status and the adverse risk they pose remains unknown.
患有射血分数降低的终末期心力衰竭（HF）的患者人数不断增加，他们改善生活质量和数量的治疗选择有限。尽管正性肌力药未能显示出生存获益，但这些药物可能会改善患者报告的健康状况，即症状、功能状态和健康相关的生活质量。我们试图回顾关于终末期 HF 患者使用正性肌力药的可用临床试验数据，并总结支持使用这些药物改善终末期 HF 患者健康状况的证据。
对评估射血分数降低的 HF 中使用正性肌力作用的随机对照试验进行了文献回顾。我们在 1980 年 1 月至 2018 年 12 月期间在 MEDLINE、SCOPUS 和 Web of Science 上搜索了使用正性肌力药作为主要疗效终点的随机对照试验，这些终点包括（1）发病率/死亡率，（2）症状，（3）功能状态或（4）健康相关生活质量的影响。有兴趣的正性肌力药包括肾上腺素能药物、磷酸二酯酶抑制剂、钙敏化剂、肌球蛋白激活剂和 SERCA2a（肌浆网 Ca-ATP 酶）调节剂。
在 26 项正性肌力药随机对照试验中，有 22 项试验测量了正性肌力药对至少一个患者报告的健康状况领域的影响。在具有患者相关健康状况结果的 22 项研究中，有 11 项（50%）评估了症状反应，15 项（68%）报告了功能容量变化，12 项（54%）报告了健康相关生活质量措施。这些试验中有 14 项（64%）至少在一个测量的健康状况领域记录了阳性结果；其中 11 项（79%）阳性研究使用了通过磷酸二酯酶抑制作用起作用的药物。
在射血分数降低的终末期 HF 中使用正性肌力药的研究中，围绕患者为中心的结局的测量缺乏标准化。正性肌力药在多大程度上可以改善患者报告的健康状况以及它们带来的不良风险仍不清楚。
