Oral Metolazone Versus Intravenous Chlorothiazide as an Adjunct to Loop Diuretics for Diuresis in Acute Decompensated Heart Failure With Reduced Ejection Fraction

Background: Thiazide diuretics are often utilized to overcome loop diuretic resistance when treating acute decompensated heart failure (ADHF). In addition to a large cost advantage, several pharmacokinetic advantages exist when administering oral metolazone (MTZ) compared with intravenous (IV) chlorothiazide (CTZ), yet many providers are reluctant to utilize an oral formulation to treat ADHF. The purpose of this study was to compare the increase in 24-hour total urine output (UOP) after adding MTZ or CTZ to IV loop diuretics (LD) in patients with heart failure with reduced ejection fraction (HFrEF). Methods and Results: From September 2013 to August 2016, 1002 patients admitted for ADHF received either MTZ or CTZ in addition to LD. Patients were excluded for heart failure with preserved ejection fraction (HFpEF) (n = 469), <24-hour LD or UOP data prior to drug initiation (n = 129), or low dose MTZ/CTZ (n = 91). A total of 168 patients were included with 64% receiving CTZ. No significant difference was observed between the increase in 24-hour total UOP after MTZ or CTZ initiation (1458 [514, 2401] mL vs 1820 [890, 2750] mL, P = .251). Conclusions: Both MTZ and CTZ similarly increased UOP when utilized as an adjunct to IV LD. These results suggest that while thiazide agents can substantially increase UOP in ADHF patients with HFrEF, MTZ and CTZ have comparable effects.