Metolazone Versus Chlorothiazide in Acute Heart Failure Patients With Diuretic Resistance and Renal Dysfunction: A Retrospective Cohort Study.

Abstract: Guidelines recommend intravenous loop diuretics as first-line therapy for patients hospitalized with acute heart failure (AHF) and volume overload. Additional agents can be used for augmentation, but there is limited guidance on agent selection. The study objective was to determine if chlorothiazide or metolazone is associated with differences in diuretic efficacy or safety in loop diuretic-resistant patients with AHF and renal dysfunction (eGFR <45 mL/min/1.73 m²). We conducted a multicenter, retrospective cohort study of patients hospitalized with AHF and renal dysfunction who received metolazone or chlorothiazide in addition to intravenous loop diuretics. The primary end point was a comparison of 24-hour urine output (UOP) between the 24 hours before and after thiazide administration. Secondary and safety end points included weight change, requirement for vasopressors or inotropes, electrolyte abnormalities, and changes in renal function. A total of 221 patients were included. The mean daily diuretic doses were chlorothiazide 632 mg and metolazone 7 mg. The mean 24-hour UOP increased more among chlorothiazide-treated (from 1668 mL to 3826 mL) versus metolazone-treated patients (from 1672 mL to 2834 mL) ( P < 0.001) after the addition of the second diuretic. Statistically significant reductions in serum creatinine were observed in the chlorothiazide group following 72 hours of treatment ( P = 0.016). More hypomagnesemia was observed in the chlorothiazide group; no differences in other electrolytes or changes in weight were observed. Overall, chlorothiazide was associated with a greater increase in 24-hour UOP than metolazone without an excess of potassium or serum creatinine derangements. However, weight changes did not differ significantly between groups. Future prospective studies are needed to confirm potential differences in diuretic response and safety.