Effect of admission oral diuretic dose on response to continuous versus bolus intravenous diuretics in acute heart failure: an analysis from diuretic optimization strategies in acute heart failure

Am Heart J. 2012 Dec;164(6):862-8. doi: 10.1016/j.ahj.2012.08.019. Epub 2012 Oct 29.


Background: Results from the DOSE-AHF study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in acute heart failure. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses.

Methods: The DOSE-AHF study randomized 308 patients within 24 hours of admission to high versus low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n = 177) versus low-dose (<120 mg furosemide equivalent, n = 131) outpatient diuretics.

Results: Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P = .01) and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P = .01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted hazard ratio 1.08 per 20-mg increment in dose, 95% CI 1.01-1.16, P = .03).

Conclusions: In acute heart failure, patients on higher diuretic doses have greater disease severity and may benefit from an initial bolus strategy.

Trial registration: ClinicalTrials.gov NCT00577135.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Creatinine / blood
  • Cystatin C / blood
  • Diuretics / administration & dosage*
  • Diuretics / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Furosemide / administration & dosage*
  • Furosemide / adverse effects
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Outpatients
  • Pain Measurement / drug effects
  • Patient Readmission
  • Peptide Fragments / blood
  • Proportional Hazards Models
  • Treatment Outcome


  • Cystatin C
  • Diuretics
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Furosemide
  • Creatinine

Associated data

  • ClinicalTrials.gov/NCT00577135