Decisions in Diuretic Resistance: Oral or Subcutaneous Furosemide in Advanced Ambulatory Heart Failure?

Objectives: The objective of this study was to explore differences in short-term clinical response, renal outcomes, and healthcare resource utilization between two non-equivalent outpatient furosemide strategies: high-dose oral solution and subcutaneous administration. Methods: This retrospective observational study included 108 consecutive outpatients with advanced heart failure (HF) and diuretic resistance treated between January 2018 and December 2024. Patients received furosemide for 5 days as oral solution (250 mg/day; n = 81) or subcutaneous infusion via elastomeric pump (100 mg/day; n = 27). Primary endpoints were changes in functional status (NYHA [New York Heart Association] class), body weight, and renal function, assessed by changes in serum creatinine and estimated glomerular filtration rate and by clinically relevant worsening renal function criteria. Secondary endpoints included NT-proBNP changes and unplanned healthcare utilization at 30 days. Results: Both strategies were associated with short-term decongestion. Weight decreased similarly in both groups, with no difference in the proportion of patients achieving weight loss (oral 90% vs. subcutaneous 89%; p = 0.854). Functional improvement was more frequently observed in the oral-solution group (99% vs. 89%; p = 0.019). Renal outcomes were comparable between strategies, with no significant changes in eGFR and a similar proportion of patients experiencing a serum creatinine increase ≥0.3 mg/dL (25.9% vs. 22.2%; p = 0.85). No significant differences were observed in NT-proBNP changes. HF-related healthcare encounters decreased during the 30 days following treatment compared with the preceding 30-day period in the oral-solution group, whereas no significant within-group change was observed in the subcutaneous group. Conclusions: In this exploratory real-world cohort of patients with advanced HF and refractory congestion, both outpatient strategies were associated with short-term decongestion, with differences observed in symptomatic response. These findings are hypothesis-generating and warrant confirmation in prospective studies using comparable dosing strategies.