TY - JOUR
T1 - Furosemide induces mortality in a rat model of chronic heart failure
AU - Rokutan, Hirofumi
AU - Suckow, Christian
AU - Von Haehling, Stephan
AU - Strassburg, Sabine
AU - Bockmeyer, Barbara
AU - Doehner, Wolfram
AU - Waller, Christiane
AU - Bauersachs, Johann
AU - Von Websky, Karoline
AU - Hocher, Berthold
AU - Anker, Stefan D.
AU - Springer, Jochen
PY - 2012/9/20
Y1 - 2012/9/20
N2 - 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.
AB - 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.
KW - Angiotensin converting enzyme inhibitor
KW - Furosemide
KW - Heart failure
KW - Loop diuretics
KW - Mortality
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U2 - 10.1016/j.ijcard.2011.03.005
DO - 10.1016/j.ijcard.2011.03.005
M3 - Article
C2 - 21450356
AN - SCOPUS:84865652341
VL - 160
SP - 20
EP - 25
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
IS - 1
ER -