October 29, 2025European Journal of Heart Failure2 citationsOpen Access
View Full PaperOutpatient Loop Diuretic Use and the Effect of Natriuresis-Guided Diuretic Therapy: A Prespecified Sub-Analysis of the PUSH-AHF Study
Structured PICO
Does natriuresis-guided diuretic therapy improve 24-h natriuresis and clinical outcomes in patients hospitalized for ADHF regardless of prior outpatient loop diuretic use?
P
Population
310 patients hospitalized for acute decompensated heart failure (ADHF), stratified by outpatient loop diuretic use (133 no prior use, 65 used 0-1 mg bumetanide, 112 used >1 mg bumetanide or equivalent).
I
Intervention
Natriuresis-guided diuretic therapy
C
Comparator
Standard of care
O
Outcome
24-h natriuresis and combined endpoint of heart failure rehospitalization or all-cause mortality at 180 dayscomposite
Natriuresis-guided diuretic therapy is effective at increasing 24-hour natriuresis in patients with acute decompensated heart failure, regardless of their prior outpatient loop diuretic dose.
Abstract
AIMS: Diuretic resistance is frequently observed in patients with acute decompensated heart failure (ADHF), specifically in those with chronic use of loop diuretics (LD). Natriuresis-guided therapy may be useful to overcome this, however it is unknown whether its effect is impacted by chronic LD use. The aim of this study was to evaluate the effect of outpatient LD use on natriuresis and clinical outcomes, and to determine whether natriuresis-guided therapy modifies these effects in patients hospitalized for ADHF. METHODS AND RESULTS: In this prespecified sub-analysis of the PUSH-AHF trial, the association between outpatient LD use, predefined primary, secondary and safety outcomes as established in the PUSH-AHF protocol, and the effect of natriuresis-guided therapy as compared with standard of care was evaluated. Patients in both arms received the first in-hospital LD dose based on renal function and outpatient LD dose. Out of 310 randomized patients, 133 (43%) had no prior LD use, 65 (21%) used 0-1 mg bumetanide and 112 (36%) used >1 mg bumetanide (or equivalent). Patients with higher outpatient LD doses had a longer history of heart failure and worse renal function (p for trend <0.001). Higher outpatient LD doses were associated with lower 24-h natriuresis (340 ± 194 mmol vs. 420 ± 200 mmol in diuretic-naïve patients, p for trend = 0.002). Natriuresis-guided therapy significantly increased 24-h natriuresis regardless of outpatient LD use (p for interaction = 0.420). No interaction between outpatient LD use, natriuresis-guided therapy and the effect on the combined endpoint of heart failure rehospitalization or all-cause mortality at 180 days was observed (p for interaction = 0.881). CONCLUSIONS: Outpatient LD use results in reduced natriuresis. However, the beneficial effects of natriuresis-guided diuretic therapy on 24-h natriuresis were consistent, regardless of previous LD use.