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

Abstract

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.

Copyright © 2012 Mosby, Inc. All rights reserved.

Figures

Figure 1

Predicted net fluid loss at 72 hours, based on a multivariate model containing qualifying furosemide dose, mode of administration (bolus or continuous infusion), and an interaction term. Similar results (e.g., greater net fluid loss at lower qualifying doses with a bolus strategy) were obtained when stratified by intravenous dose intensity (data not shown).

Figure 2

Kaplan-Meier survival curves for death or re-hospitalization at 60 days, stratified by outpatient furosemide dose.