BACKGROUND: Heart failure (HF) in elderly patients with concurrent hypotension presents a therapeutic challenge due to limited standard HF therapies' applicability. Recombinant human brain natriuretic peptide (rhBNP) and vasoactive medications have shown potential in HF management, but their combined efficacy in elderly patients with HF and hypotension remains understudied. METHODS: This retrospective cohort study included elderly HF patients with hypotension who received rhBNP alone (Group A, n = 68), rhBNP with dobutamine (Group B, n = 74), or rhBNP with dopamine (Group C, n = 71). Biomarker responses, cardiac function, adverse events, and cost implications were compared among the groups using statistical analysis. RESULTS: The combination therapy groups (B and C) showed significantly lower NT-proBNP levels compared to the rhBNP-alone group (P <
0.001). Troponin I levels were also lower in the combination therapy groups compared to the rhBNP-alone group (P <
0.05). Left ventricular ejection fraction (LVEF) was significantly higher in the combination therapy groups compared to the rhBNP-alone group (P <
0.05). No significant differences were found in adverse events or cost implications among the groups. CONCLUSION: Combining rhBNP with vasoactive medications in elderly patients with HF and hypotension led to notable reductions in biomarkers and improvements in LVEF without significant differences in adverse events or cost implications. These findings support the potential utility of combined rhBNP and vasoactive medications therapy in optimizing HF management in this patient population, warranting further investigation through prospective studies. TRIAL REGISTRATION: Not applicable. CLINICAL TRIAL NUMBER: Not applicable.