Furosemide induces mortality in a rat model of chronic heart failure

Hirofumi Rokutan, Christian Suckow, Stephan Von Haehling, Sabine Strassburg, Barbara Bockmeyer, Wolfram Doehner, Christiane Waller, Johann Bauersachs, Karoline Von Websky, Berthold Hocher, Stefan D. Anker, Jochen Springer

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: 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. Methods and 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 (10 mg/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 (1 mg/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). Conclusion: 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.

Original languageEnglish
Pages (from-to)20-25
Number of pages6
JournalInternational Journal of Cardiology
Volume160
Issue number1
DOIs
Publication statusPublished - Sep 20 2012

Keywords

  • Angiotensin converting enzyme inhibitor
  • Furosemide
  • Heart failure
  • Loop diuretics
  • Mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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