Comparison of Bumetanide- and Metolazone-Based Diuretic Regimens to Furosemide in Acute Heart Failure

Introduction: Limited data exist comparing the efficacy and safety of bumetanide- or metolazone-based diuretic regimens to furosemide in acute heart failure (HF). Our purpose was to evaluate the comparative effect on urine output (UO) and renal function between these regimens. Methods: A retrospective study of hospitalized HF patients treated with continuous infusion furosemide (CIF), combination furosemide plus metolazone (F + M), or continuous infusion bumetanide (CIB). Primary end points were between regimen comparisons for change in mean hourly UO versus baseline and incidence of worsening renal function. Results: Data on 242 patients with acute HF (age 58 ± 12 years, 63% male, left ventricular ejection fraction 38% ± 17%) were analyzed (160 CIF, 42 F + M, 40 CIB). The mean duration of diuretic regimens was 41 ± 32 hours. Compared to baseline, all regimens increased mean hourly UO ( P < .0001 for all), with greater increases with F + M (109 ± 171 mL) and CIB (90 ± 90 mL) compared to CIF (48 ± 103 mL; P = .009). Incidence of worsening renal function was not different between regimens; however, blood urea nitrogen (BUN) tended to increase more with F + M (4.4 ± 9.8 mg/dL) and CIB (4.3 ± 9.7 mg/dL) than CIF (1.8 ± 10.8 mg/dL), P = .09. The incidence of hyponatremia was higher with F + M and CIB. Differences in UO, BUN, and hyponatremia were retained in the subgroup analysis limited to patients with baseline serum creatinine <1.5 mg/dL, where renal function between the groups was not different. Conclusion: Compared to CIF, F + M or CIB was associated with greater increases in UO. No difference in the incidence of worsening renal function was found; however, electrolyte abnormalities may be more prevalent when furosemide is combined with metolazone or when bumetanide is used. These therapeutic differences warrant prospective study.