Burnett Heather, Earley Amy, Voors Adriaan A, Senni Michele, McMurray John J V, Deschaseaux Celine, Cope Shannon
From the Mapi, Health Economics and Outcomes Research, Dundas, Canada (H.B.); Mapi, Health Economics and Outcomes Research, Boston, MA (A.E.); Department of Cardiology, University of Groningen, The Netherlands (A.A.V.); Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy (M.S.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, UK (J.J.V.M.); Global Patient Access, Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland (C.D.); and Mapi, Health Economics and Outcomes Research, Toronto, Canada (S.C.).
Circ Heart Fail. 2017 Jan;10(1):e003529. doi: 10.1161/CIRCHEARTFAILURE.116.003529.
Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor-neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction.
A systematic literature review identified 57 randomized controlled trials published between 1987 and 2015, which were compared in terms of study and patient characteristics, baseline risk, outcome definitions, and the observed treatment effects. Despite differences identified in terms of study duration, New York Heart Association class, ejection fraction, and use of background digoxin, a network meta-analysis was considered feasible and all trials were analyzed simultaneously. The random-effects network meta-analysis suggested that the combination of ACEI+BB+MRA was associated with a 56% reduction in mortality versus placebo (hazard ratio 0.44, 95% credible interval 0.26-0.66); ARNI+BB+MRA was associated with the greatest reduction in all-cause mortality versus placebo (hazard ratio 0.37, 95% credible interval 0.19-0.65). A sensitivity analysis that did not account for background therapy suggested that ARNI monotherapy is more efficacious than ACEI or ARB monotherapy.
The network meta-analysis showed that treatment with ACEI, ARB, BB, MRA, and ARNI and their combinations were better than the treatment with placebo in reducing all-cause mortality, with the exception of ARB monotherapy and ARB plus ACEI. The combination of ARNI+BB+MRA resulted in the greatest mortality reduction.
射血分数降低的心力衰竭患者的治疗方法，包括血管紧张素转换酶抑制剂（ACEI）、血管紧张素受体阻滞剂（ARB）、β受体阻滞剂（BB）、盐皮质激素受体拮抗剂（MRA）和血管紧张素受体脑啡肽酶抑制剂（ARNI），尚未进行过直接比较的研究。这项网络荟萃分析旨在比较这些药物及其组合在射血分数降低的心力衰竭患者全因死亡率方面的疗效。
一项系统的文献综述确定了1987年至2015年间发表的57项随机对照试验，对这些试验在研究和患者特征、基线风险、结局定义以及观察到的治疗效果方面进行了比较。尽管在研究持续时间、纽约心脏协会分级、射血分数以及背景地高辛的使用方面存在差异，但认为网络荟萃分析是可行的，并对所有试验进行了同步分析。随机效应网络荟萃分析表明，与安慰剂相比，ACEI+BB+MRA联合使用可使死亡率降低56%（风险比0.44，95%可信区间0.26-0.66）；ARNI+BB+MRA与安慰剂相比，全因死亡率降低幅度最大（风险比0.37，95%可信区间0.19-0.65）。一项未考虑背景治疗的敏感性分析表明，ARNI单药治疗比ACEI或ARB单药治疗更有效。
网络荟萃分析表明，ACEI、ARB、BB、MRA和ARNI及其组合治疗在降低全因死亡率方面优于安慰剂治疗，但ARB单药治疗以及ARB加ACEI除外。ARNI+BB+MRA联合使用导致死亡率降低幅度最大。
