Beldhuis Iris E, Streng Koen W, Ter Maaten Jozine M, Voors Adriaan A, van der Meer Peter, Rossignol Patrick, McMurray John J V, Damman Kevin
From the Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (I.E.B., K.W.S., J.M.T.M., A.A.V., P.v.d.M., K.D.); Inserm, Centre d'Investigations Cliniques-Plurithématique 1433, Inserm U1116; CHRU Nancy, France (P.R.); Université de Lorraine, F-CRIN INI-CRCT Network, Nancy, France (P.R.); and British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.M.).
Circ Heart Fail. 2017 Feb;10(2). doi: 10.1161/CIRCHEARTFAILURE.116.003588.
Renin-angiotensin aldosterone system (RAAS) inhibitors significantly improve outcome in heart failure (HF) patients with reduced ejection fraction (HFREF), irrespective of the occurrence of worsening renal function (WRF). However, in HF patients with preserved ejection fraction (HFPEF), RAAS inhibitors have not been shown to improve outcome but are still frequently prescribed.
Random effect meta-analysis was performed to investigate the relationship between RAAS inhibitor therapy, WRF in both HF phenotypes, and mortality. Studies were selected based on literature search in MEDLNE and included randomized, placebo controlled trials of RAAS inhibitors in chronic HF. The primary outcome consisted of the interaction analysis for the association between RAAS inhibition-induced WRF, HF phenotype and outcome. A total of 8 studies (6 HFREF and 2 HFPEF, including 28 961 patients) were included in our analysis. WRF was more frequent in the RAAS inhibitor group, compared with the placebo group, in both HFREF and HFPEF. In HFREF, WRF induced by RAAS inhibitor therapy was associated with a less increased relative risk of mortality (relative risk, 1.19 (1.08-1.31); <0.001), compared with WRF induced by placebo (relative risk, 1.48 (1.35-1.62); <0.001; for interaction 0.005). In contrast, WRF induced by RAAS inhibitor therapy was strongly associated with worse outcomes in HFPEF (relative risk, 1.78 (1.43-2.21); <0.001), whereas placebo-induced WRF was not (relative risk, 1.25 (0.88-1.77); =0.21; for interaction 0.002).
RAAS inhibitors induce renal dysfunction in both HFREF and HFPEF. However, in contrast to patients with HFREF where mortality increase with WRF is small, HFPEF patients with RAAS inhibitor-induced WRF have an increased mortality risk, without experiencing improved outcome with RAAS inhibition.
肾素-血管紧张素-醛固酮系统（RAAS）抑制剂可显著改善射血分数降低的心力衰竭（HFREF）患者的预后，无论肾功能恶化（WRF）是否发生。然而，在射血分数保留的心力衰竭（HFPEF）患者中，RAAS抑制剂尚未显示能改善预后，但仍经常被处方使用。
进行随机效应荟萃分析，以研究RAAS抑制剂治疗、两种HF表型中的WRF与死亡率之间的关系。基于MEDLNE中的文献检索选择研究，纳入RAAS抑制剂治疗慢性HF的随机、安慰剂对照试验。主要结局包括RAAS抑制诱导的WRF、HF表型与结局之间关联的交互分析。我们的分析共纳入8项研究（6项HFREF和2项HFPEF，包括28961例患者）。在HFREF和HFPEF中，与安慰剂组相比，RAAS抑制剂组的WRF更常见。在HFREF中，与安慰剂诱导的WRF（相对风险，1.48（1.35 - 1.62）；P < 0.001）相比，RAAS抑制剂治疗诱导的WRF与死亡率相对风险增加较少相关（相对风险，1.19（1.08 - 1.31）；P < 0.001；交互作用P = 0.005）。相比之下，RAAS抑制剂治疗诱导的WRF与HFPEF中更差的结局密切相关（相对风险，1.78（1.43 - 2.21）；P < 0.001），而安慰剂诱导的WRF则不然（相对风险，1.25（0.88 - 1.77）；P = 0.21；交互作用P = 0.002）。
RAAS抑制剂在HFREF和HFPEF中均会诱导肾功能不全。然而，与HFREF患者中WRF导致的死亡率小幅增加不同，RAAS抑制剂诱导WRF的HFPEF患者死亡风险增加，且RAAS抑制并未改善其预后。
