TY  - JOUR
A1  - Rokutan, Hirofumi
A1  - Suckow, Christian
A1  - von Hähling, Stephan
A1  - Strassburg, Sabine
A1  - Bockmeyer, Barbara
A1  - Döhner, Wolfram
A1  - Waller, Christiane
A1  - Bauersachs, Johann
A1  - von Websky, Karoline
A1  - Hocher, Berthold
A1  - Anker, Stefan D.
A1  - Springer, Jochen
T1  - Furosemide induces mortality in a rat model of chronic heart failure
JF  - International journal of cardiology
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.
KW  - Angiotensin converting enzyme inhibitor
KW  - Furosemide
KW  - Heart failure
KW  - Loop diuretics
KW  - Mortality
Y1  - 2012
U6  - https://doi.org/10.1016/j.ijcard.2011.03.005
SN  - 0167-5273
VL  - 160
IS  - 1
SP  - 20
EP  - 25
PB  - Elsevier
CY  - Clare
ER  -