title: Renin-Angiotensin System Inhibition, Worsening Renal Function, and Outcome in Heart Failure Patients With Reduced and Preserved Ejection Fraction: A Meta-Analysis of Published Study Data.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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);P<0.001), compared with WRF induced by placebo (relative risk, 1.48 (1.35-1.62);P<0.001;Pfor 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);P<0.001), whereas placebo-induced WRF was not (relative risk, 1.25 (0.88-1.77);P=0.21;Pfor interaction 0.002).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.).
authors.forename: Iris E
authors.initials: IE
authors.lastname: Beldhuis
authors.affiliation: 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.).
authors.forename: Koen W
authors.initials: KW
authors.lastname: Streng
authors.affiliation: 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.).
authors.forename: Jozine M
authors.initials: JM
authors.lastname: Ter Maaten
authors.affiliation: 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.).
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: 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.).
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
authors.affiliation: 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.).
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.affiliation: 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.).
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: 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.). k.damman@umcg.nl.
authors.forename: Kevin
authors.initials: K
authors.lastname: Damman
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D016009:Chi-Square Distribution; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects*; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: MEDLINE; heart failure; phenotype; prognosis; renin–angiotensin system