Supplementary Material for: Evaluation of Patients with Heart Failure with Reduced Ejection Fraction Treated with Bumetanide versus Torsemide

Introduction
Limited evidence guides clinicians regarding the agent selection between bumetanide and torsemide in patients with heart failure (HF). The present study aimed to compare the efficacy and safety profile of bumetanide and torsemide in patients with HF.

Methods
Patients aged > 18 years with HF with reduced ejection fraction (HFrEF) receiving either bumetanide or torsemide were included from the TriNetX research network. Patients with end-stage renal disease were excluded from this study. The primary outcome was all-cause mortality, and secondary outcomes included all-cause hospitalization or emergency department visits, acute kidney injury, or hypokalemia over one- year follow-up period.

Results
After propensity score matching, 16,277 patients in each group were included. The use of bumetanide was significantly associated with a higher risk of all-cause mortality (19.7 vs. 16.0 %; OR 1.28; 95% CI [1,21, 1.36]) compared to the torsemide group. The use of bumetanide was also significantly associated with higher risks of all-cause hospitalization or emergency department visits (53.3 vs. 48.3%; OR 1.22 95% CI [1.17, 1.28]), acute kidney injury (33.4 vs. 27.1 %; OR 1.35; 95% CI [1.29, 1.42]), and hypokalemia (16.6 vs. 13.7%; OR 1.21, 95% CI [1.17, 1.33]) compared to the torsemide group.

Conclusion
The use of torsemide in patients with HFrEF is associated with lower risks of clinical outcomes than bumetanide. Further investigation of this association is warranted in clinical trials.