title: Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure.
abstract: Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF).
  
  
  
  To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF.
  
  
  
  Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders.
  
  
  
  The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P < .001), and the best cutoff was >40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P < .001) or high dose (HR = 19.8; 95% CI: 7.9-49.6; P < .001) had a higher risk of mortality compared to those receiving a low dose. Patients receiving >40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039).
  
  
  
  Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.
authors: 1 Heart Failure Unit, Cardiology Department, Lisbon North Hospital Centre, Pulido Valente Hospital, Lisbon, Portugal.
authors: Luis
authors: L
authors: Sargento
authors: 2 Internal Medicine, Lisbon North Hospital Centre, Pulido Valente Hospital, Lisbon, Portugal.
authors: Andre Vicente
authors: AV
authors: Simões
authors: 1 Heart Failure Unit, Cardiology Department, Lisbon North Hospital Centre, Pulido Valente Hospital, Lisbon, Portugal.
authors: Susana
authors: S
authors: Longo
authors: 1 Heart Failure Unit, Cardiology Department, Lisbon North Hospital Centre, Pulido Valente Hospital, Lisbon, Portugal.
authors: Nuno
authors: N
authors: Lousada
authors: 1 Heart Failure Unit, Cardiology Department, Lisbon North Hospital Centre, Pulido Valente Hospital, Lisbon, Portugal.
authors: Roberto Palma Dos
authors: RP
authors: Reis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005665:Furosemide / Q000008:administration & dosage* / Q000009:adverse effects; D054143:Heart Failure, Systolic / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D016016:Proportional Hazards Models; D012372:ROC Curve; D012307:Risk Factors; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D049994:Sodium Potassium Chloride Symporter Inhibitors; D005665:Furosemide
keywords: furosemide; survival; systolic heart failure