title: Association between renin-angiotensin system antagonist use and mortality in heart failure with severe renal insufficiency: a prospective propensity score-matched cohort study.
abstract: OBJECTIVE
  In heart failure (HF) with reduced ejection fraction (EF), renin-angiotensin receptor (RAS) antagonists reduce mortality. However, severe renal insufficiency was an exclusion criterion in trials. We tested the hypothesis that RAS antagonists are associated with reduced mortality also in HF with severe renal insufficiency.
  
  
  RESULTS
  We studied patients with EF ≤39% registered in the prospective Swedish Heart Failure Registry. In patients with creatinine >221 µmol/L or creatinine clearance <30 mL/min, propensity scores for RAS-antagonist use were derived from 36 variables. The association between RAS antagonist use and all-cause mortality was assessed with Cox regression in a cohort matched 1:1 based on age and propensity score. To assess consistency, we performed the same analysis as a 'positive control' in patients without severe renal insufficiency. Between 2000 and 2013, there were 24 283 patients of which 2410 [age, mean (SD), 82 (9), 45% women] had creatinine >221 µmol/L or creatinine clearance <30 mL/min and were treated (n = 1602) or not treated (n = 808) with RAS antagonists. In the matched cohort of 602 vs. 602 patients [age 83 (8), 42% women], RAS antagonist use was associated with 55% [95% confidence interval (CI) 51-59] vs. 45% (41-49) 1-year survival, P < 0.001, with a hazard ratio (HR) for mortality of 0.76 (95% CI 0.67-0.86, P < 0.001). In positive control patients without severe renal insufficiency [n = 21 873; age 71 (12), 27% women], the matched HR was 0.79 (95% CI 0.72-0.86, P < 0.001).
  
  
  CONCLUSIONS
  In HF with severe renal insufficiency, the use of RAS antagonists was associated with lower all-cause mortality. Prospective randomized trials are needed before these findings can be applied to clinical practice.
authors.affiliation: Department of Medicine, Unit of Cardiology, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Edner
authors.affiliation: Department of Clinical Science and Education, SöS, Karolinska Institutet, 11883 Stockholm, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Benson
authors.affiliation: Division of Cardiovascular Medicine, Faculty of Health Sciences, Department of Medicine and Health Sciences, Department of Cardiology UHL, Linköping University, County Council of Östergötland, 58191 Linköping, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Dahlström
authors.affiliation: Department of Medicine, Unit of Cardiology, Karolinska Institutet, 17177 Stockholm, Sweden Department of Cardiology, N3:06, Karolinska University Hospital, 17176 Stockholm, Sweden lars.lund@alumni.duke.edu.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lund
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D059347:Cardio-Renal Syndrome / Q000209:etiology; D002423:Cause of Death; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D057216:Propensity Score; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000209:etiology; D012084:Renin-Angiotensin System / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: ACE-inhibitor; Angiotensin receptor blocker; Chronic kidney disease; Creatinine clearance; Heart failure; Renal insufficiency; Renin–angiotensin system antagonists