Diuretic efficiency of a single dose of subcutaneous versus oral furosemide after heart failure hospitalization across diuretic resistance strata: A pilot randomized controlled trial

Abstract

Aims: Diuretic resistance (DR) in heart failure (HF) is associated with worse outcomes. Furoscix®, a self-administered subcutaneous (sc) furosemide injection administered via on-body infusor, is approved for HF congestion relief. However, its efficacy in patients with DR post-HF hospitalization remains unknown.

Methods and results: In this open-label pilot randomized controlled trial, 70 participants were randomized within 14 days post-HF hospitalization to receive a single dose of 80 mg sc furosemide or home oral dose furosemide. Enrolment was stratified by presence of DR (admission BAN-ADHF score ≥12) with a 2:1 enrolment of those with versus without DR. Key outcomes included diuretic efficiency, the total urine output per mg of diuretic administered, and peak urine sodium within 8 h of dose administration. Treatment effects were calculated as the difference in estimated marginal means across study groups and DR strata using linear mixed-effect models. Overall, 70 participants were enrolled (57 years, 27% female, 70% Black, 79% with HF with reduced ejection fraction). Participants with DR (n = 46) had worse kidney function, higher N-terminal pro-B-type natriuretic peptide, and higher home diuretic dose. Among participants with DR, sc furosemide versus oral furosemide led to significantly greater diuretic efficiency (34.0 vs. 22.6 ml/mg, p = 0.002) and peak urine sodium (100 vs. 83 mmol/L, p = 0.029), while participants without DR had similar diuretic efficiency (29.8 vs. 30.1 ml/mg, p = 0.94) and peak urine sodium (96 vs. 95 mmol/L, p = 0.93) across both treatments. DR significantly modified the effect of sc versus oral furosemide on diuretic efficiency (p_interaction: treatment × diuretic resistance = 0.022).

Conclusion: Single-dose sc furosemide was associated with greater diuretic efficiency and peak urine sodium than oral furosemide in participants with DR discharged following recent HF hospitalization.

Keywords: Diuretic resistance; Heart failure; Subcutaneous furosemide.

Figure 1

(A) Diuretic efficiency over 8‐h follow‐up and (B) peak urine sodium concentration at 4 h after subcutaneous (sc) versus oral furosemide treatment stratified by diuretic resistance (DR). Values shown are estimated marginal means and 95% confidence intervals from linear mixed‐effect models.

Figure 2

Cumulative urine output per milligram of furosemide over the 8‐h study period stratified by treatment arm and diuretic resistance (DR) strata. Solid lines represent the estimated marginal means for each group from a linear mixed‐effects model.

Figure 3

Urine sodium concentration after subcutaneous (sc) versus oral furosemide stratified by those (A) with diuretic resistance (DR) and (B) without DR. Urine sodium concentrations are shown at hours 2, 4, 6, and 8 after treatment with either sc or oral furosemide stratified by DR. Values shown are estimated marginal means and 95% confidence intervals from linear mixed‐effect models.