title: Worsening renal function and outcome in heart failure patients with preserved ejection fraction and the impact of angiotensin receptor blocker treatment.
abstract: BACKGROUND
  Worsening renal function (WRF) associated with renin-angiotensin-aldosterone system (RAAS) inhibition does not confer excess risk in heart failure patients with reduced ejection fraction (HFrEF).
  
  
  OBJECTIVE
  The goal of this study was to investigate the relationship between WRF and outcomes in heart failure patients with preserved ejection fraction (HFpEF) and the interaction with RAAS blockade.
  
  
  METHODS
  In 3,595 patients included in the I-PRESERVE (Irbesartan in Heart Failure With Preserved Ejection Fraction) trial, change in estimated glomerular filtration rate (eGFR) and development of WRF after initiation of irbesartan or placebo were examined. We examined the association between WRF and the first occurrence of cardiovascular death or heart failure hospitalization (primary outcome in this analysis) and the interaction with randomized treatment.
  
  
  RESULTS
  Estimated GFR decreased early with irbesartan treatment and remained significantly lower than in the placebo group. WRF developed in 229 (6.4%) patients and occurred more frequently with irbesartan treatment (8% vs. 4%). Overall, WRF was associated with an increased risk of the primary outcome (adjusted hazard ratio [HR]: 1.43; 95% confidence interval [CI]: 1.10 to 1.85; p = 0.008). Although the risk related to WRF was greater in the irbesartan group (HR: 1.66; 95% CI: 1.21 to 2.28; p = 0.002) than with placebo (HR: 1.09; 95% CI: 0.66 to 1.79; p = 0.73), the interaction between treatment and WRF on outcome was not significant in an adjusted analysis.
  
  
  CONCLUSIONS
  The incidence of WRF in HFpEF was similar to that previously reported in HFrEF but more frequent with irbesartan than with placebo. WRF after initiation of irbesartan treatment in HFpEF was associated with excess risk, in contrast to WRF occurring with RAAS blockade in HFrEF.
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: k.damman@umcg.nl.
authors.forename: Kevin
authors.initials: K
authors.lastname: Damman
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Perez
authors.affiliation: Veterans Affairs Medical Center and University of Minnesota, Minneapolis, Minnesota.
authors.forename: Inder S
authors.initials: IS
authors.lastname: Anand
authors.affiliation: Université Paris 6 and Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.affiliation: Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Robert S
authors.initials: RS
authors.lastname: McKelvie
authors.affiliation: Ralph H. Johnson Veterans Affairs Medical Center and Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zile
authors.affiliation: University of California, San Francisco, and San Francisco Veterans Affairs Medical Center, San Francisco, California.
authors.forename: Barrie
authors.initials: B
authors.lastname: Massie
authors.affiliation: Georgetown University and Washington DC Veterans Affairs Medical Center, Washington, DC.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Carson
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D000077405:Irbesartan; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013318:Stroke Volume; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan
keywords: HFpEF; angiotensin receptor blocker; prognosis; worsening renal function