title: Worsening renal function and outcome in heart failure patients with reduced and preserved ejection fraction and the impact of angiotensin receptor blocker treatment: data from the CHARM-study programme.
abstract: We investigated the association between worsening renal function (WRF) that occurs during renin-angiotensin-aldosterone system inhibition initation and outcome in heart failure (HF) patients with preserved ejection fraction (HFPEF) and compared this with HF patients with reduced ejection fraction (HFREF).
  
  
  
  We examined changes in estimated glomerular filtration rate (GFR) and the relationship between WRF (defined as ≥26.5 µmol/L and ≥25% increase in serum creatinine from baseline to 6 weeks) and outcome, according to randomized treatment, in patients with HFREF (EF <45%; n = 1569) and HFPEF (EF ≥45%; n = 836) in the CHARM programme. The primary outcome was cardiovascular death or HF hospitalization. Estimated GFR decreased 9.0 ± 21 vs. 4.0 ± 21 mL/min/1.73 m2with candesartan and placebo, respectively, and this was similar in HFREF and HFPEF. WRF developed more frequently with candesartan, 16% vs. 7%, P < 0.001, with similar findings in patients with HFREF and HFPEF. WRF was associated with a higher risk of the primary outcome: multivariable hazard ratio (HR) 1.26, 95% confidence interval 1.03-1.54, P = 0.022, in both treatment groups, and in both HFREF and HFPEF (P for interaction 0.98). In HFREF, WRF was mostly related to HF hospitalization, while in HFPEF, WRF seemed more associated with mortality.
  
  
  
  GFR decreased more and WRF was more common with candesartan compared with placebo, and this was similar in HFREF and HFPEF. WRF was associated with worse outcomes in HFREF and HFPEF. Although no formal interaction was present, the association between candesartan treatment, WRF, and type of clinical outcome was slightly different between HFREF and HFPEF.
authors.affiliation: British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.|University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Kevin
authors.initials: K
authors.lastname: Damman
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.affiliation: University of Gothenburg, Gothenburg, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Young
authors.affiliation: Faculty of Medicine, University of Montreal, Montreal, Canada.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Rouleau
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.affiliation: British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D003404:Creatinine / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000453:epidemiology* / Q000378:metabolism; D013318:Stroke Volume; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D003404:Creatinine; C081643:candesartan
keywords: Angiotensin receptor blocker; HFPEF; HFREF; Prognosis; Worsening renal function