Diuretic strategies in patients with acute decompensated heart failure

N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419.

Abstract

Background: Loop diuretics are an essential component of therapy for patients with acute decompensated heart failure, but there are few prospective data to guide their use.

Methods: In a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient's previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients' global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours.

Results: In the comparison of bolus with continuous infusion, there was no significant difference in patients' global assessment of symptoms (mean AUC, 4236±1440 and 4373±1404, respectively; P=0.47) or in the mean change in the creatinine level (0.05±0.3 mg per deciliter [4.4±26.5 μmol per liter] and 0.07±0.3 mg per deciliter [6.2±26.5 μmol per liter], respectively; P=0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients' global assessment of symptoms in the high-dose group (mean AUC, 4430±1401 vs. 4171±1436; P=0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08±0.3 mg per deciliter [7.1±26.5 μmol per liter] with the high-dose strategy and 0.04±0.3 mg per deciliter [3.5±26.5 μmol per liter] with the low-dose strategy, P=0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function.

Conclusions: Among patients with acute decompensated heart failure, there were no significant differences in patients' global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Aged
  • Area Under Curve
  • Creatinine / blood
  • Diuretics / administration & dosage*
  • Diuretics / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Dyspnea / etiology
  • Female
  • Furosemide / administration & dosage*
  • Furosemide / adverse effects
  • Heart Failure / blood
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Humans
  • Infusions, Intravenous
  • Injections, Intravenous
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Sodium Potassium Chloride Symporter Inhibitors / administration & dosage*
  • Sodium Potassium Chloride Symporter Inhibitors / adverse effects

Substances

  • Diuretics
  • Sodium Potassium Chloride Symporter Inhibitors
  • Furosemide
  • Creatinine

Associated data

  • ClinicalTrials.gov/NCT00577135

Grants and funding