title: Diuretic dose and long-term outcomes in elderly patients with heart failure after hospitalization.
abstract: BACKGROUND
  The array of outcomes according to longitudinal furosemide doses in heart failure (HF) have not been evaluated. We examined the relationship of dynamic furosemide dose with mortality and hospitalizations for cardiovascular disease and renal dysfunction.
  
  
  METHODS
  Among elderly patients with HF (>or=65 years) newly discharged from hospital, dynamic furosemide exposure was determined by examining dose fluctuations up to 5 years of follow-up using the Ontario Drug Benefit pharmacare database. Dynamic furosemide exposures were classified as low dose (LD; 1-59 mg/d), medium dose (MD; 60-119 mg/d), or high dose (HD; >or=120 mg/d). Outcomes were assessed by modeling furosemide exposure as a time-dependent covariate.
  
  
  RESULTS
  Among 4,406 patients (78.4 +/- 7.0 years; 50.5% male), 46% changed furosemide dose categories within 1 year, and 63% changed dose categories over the follow-up period. High-dose furosemide patients were younger, were mostly male, and exhibited more ischemic or valvular disease, diabetes, atrial fibrillation, hypotension, hyponatremia, and higher baseline creatinine than LD. Compared with LD, MD exposure was associated with increased mortality with adjusted hazard ratio 1.96 (95% CI 1.79-2.15), whereas HD exposure conferred greater mortality risk with hazard ratio 3.00 (95% CI 2.72-3.31) after multiple covariate adjustment (both P < .001). Adjusted risks of hospitalization for HF (MD: 1.24 [95% CI 1.12-1.38] and HD: 1.43 [95% CI 1.26-1.63]), renal dysfunction (MD: 1.56 [95% CI 1.38-1.76] and HD: 2.16 [95% CI 1.88-2.49]), and arrhythmias (MD: 1.15 [95% CI 1.03-1.30] and HD: 1.45 [95% CI 1.27-1.66]) were also higher with increasing furosemide exposure.
  
  
  CONCLUSIONS
  Exposure to higher furosemide doses is associated with worsened outcomes and is broadly predictive of death and morbidity.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Husam M
authors.initials: HM
authors.lastname: Abdel-Qadir
authors.forename: Jack V
authors.initials: JV
authors.lastname: Tu
authors.forename: Lingsong
authors.initials: L
authors.lastname: Yun
authors.forename: Peter C
authors.initials: PC
authors.lastname: Austin
authors.forename: Gary E
authors.initials: GE
authors.lastname: Newton
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004232:Diuretics / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005665:Furosemide / Q000008:administration & dosage*; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D008297:Male; D010359:Patient Readmission / Q000706:statistics & numerical data; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D004232:Diuretics; D005665:Furosemide