title: High furosemide dose has detrimental effects on survival of patients with stable heart failure.
abstract: BACKGROUND
  High doses of furosemide for heart failure (HF) have been correlated with an increased mortality, though whether they are a marker of disease severity or an independent predictor is unknown. We hypothesized that, in patients presenting with stable HF, the likelihood of long-term major adverse clinical events is increased by higher furosemide doses.
  
  
  METHODS
  We retrospectively recorded the doses of furosemide prescribed to 173 consecutive, clinically stable patients during a first ambulatory HF department visit. The low-dose group included 103 patients treated with 80 mg and the high-dose group included 70 patients treated with >80 mg of furosemide daily. Proportional hazard regression analyses were performed with single and multiple variables in search of correlates of long-term adverse clinical events. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated.
  
  
  RESULTS
  The baseline characteristics of the 2 groups were similar, except for estimated glomerular filtration rate, which was higher in the low- than the high-dose group (72.9 ± 19.4 vs. 60.8 ± 22.0 mL/min/ m2, p<0.001). The 3-year survival free from the composite endpoint was significantly higher in the lowdose group than in the high-dose group (93.1% vs. 60.0%, p<0.001). By multiple variable analysis, highdose furosemide was an independent predictor of an adverse outcome at 3 years (adjusted HR: 15.25; 95% CI:1.06-219.39, p=0.045). The incidence of deterioration of renal function and episodes of hypokalemia during follow up was also higher in the high furosemide dose (73.2% vs. 48.3, p=0.003, and 43.1% vs. 6.5%, p<0.001, respectively).
  
  
  CONCLUSIONS
  High doses of furosemide administered in order to stabilize HF patients and continued thereafter are associated with an adverse clinical outcome.
authors: Third Department of Cardiology, University of Athens School of Medicine, Athens, Greece.
authors: Chris J
authors: CJ
authors: Kapelios
authors: Elisabeth
authors: E
authors: Kaldara
authors: Argyrios
authors: A
authors: Ntalianis
authors: Vasilios
authors: V
authors: Sousonis
authors: Evangelos
authors: E
authors: Repasos
authors: Titika
authors: T
authors: Sfakianaki
authors: Styliani
authors: S
authors: Vakrou
authors: Chris
authors: C
authors: Pantsios
authors: John N
authors: JN
authors: Nanas
authors: John V
authors: JV
authors: Terrovitis
mesh_terms: D000328:Adult; D000368:Aged; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005665:Furosemide / Q000008:administration & dosage / Q000009:adverse effects; D006115:Greece / Q000453:epidemiology; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced / Q000453:epidemiology; D015994:Incidence; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D008875:Middle Aged; D010043:Outcome and Process Assessment, Health Care; D062072:Patient Acuity; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D013995:Time
chemical_list: D004232:Diuretics; D005665:Furosemide