title: Furosemide induces mortality in a rat model of chronic heart failure.
abstract: OBJECTIVE
  In an experimental heart failure model, we tested the hypothesis that furosemide causes excess mortality.
  
  
  BACKGROUND
  Post-hoc analysis of large clinical heart failure trails revealed that furosemide treatment might be associated with worsening of morbidity and even mortality in heart failure patients.
  
  
  RESULTS
  Myocardial infarction was induced in 7 ± 1 week old male Wistar rats by ligation of the left coronary artery. In study 1, animals were randomly assigned to treatment with furosemide (10mg/kg/d via drinking water, n=33) or placebo (n=33) starting 18 days after surgery. In study 2, animals received furosemide from day 18 and were then randomized to ongoing treatment with either furosemide only (n=38) or furosemide plus ACE-inhibitor Ramipril (1mg/kg/d, n=38) starting on day 42. In study 1 survival rate in the furosemide group was lower than in the placebo group (hazard ratio {HR} 3.39, 95% confidence interval {CI} 1.14 to 10.09, p=0.028). The furosemide group had a lower body weight (-6%, p=0.028) at the end of the study and a higher sclerosis index of the glomeruli (+9%, p=0.026) than the placebo group. Wet lung weight, infarct size, and cardiac function were similar between the groups. In study 2, the furosemide group had a higher mortality rate than the furosemide+ramipril group (HR 4.55, 95% CI 2.0 to 10.0, p=0.0003).
  
  
  CONCLUSIONS
  In our rat model of heart failure furosemide, provided at a standard dose, was associated with increased mortality. This increased mortality could be prevented by additional administration of an ACE-inhibitor.
authors: Center for Cardiovascular Research, Charité Medical School, Campus Mitte, Berlin, Germany.
authors: Hirofumi
authors: H
authors: Rokutan
authors: Christian
authors: C
authors: Suckow
authors: Stephan
authors: S
authors: von Haehling
authors: Sabine
authors: S
authors: Strassburg
authors: Barbara
authors: B
authors: Bockmeyer
authors: Wolfram
authors: W
authors: Doehner
authors: Christiane
authors: C
authors: Waller
authors: Johann
authors: J
authors: Bauersachs
authors: Karoline
authors: K
authors: von Websky
authors: Berthold
authors: B
authors: Hocher
authors: Stefan D
authors: SD
authors: Anker
authors: Jochen
authors: J
authors: Springer
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004232:Diuretics / Q000009:adverse effects* / Q000627:therapeutic use; D004452:Echocardiography; D005665:Furosemide / Q000009:adverse effects* / Q000627:therapeutic use; D006333:Heart Failure / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control; D006439:Hemodynamics; D008279:Magnetic Resonance Imaging; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D005665:Furosemide