Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure

OBJECTIVES This study compared combination diuretic strategies in acute heart failure (AHF) complicated by diuretic resistance (DR). BACKGROUND Combination diuretic regimens to overcome loop DR are commonly used but with limited evidence. METHODS This study was a randomized, double-blinded trial in 60 patients hospitalized with AHF and intravenous (IV) loop DR. Patients were randomized to oral metolazone, IV chlorothiazide, or tolvaptan therapy. All patients received concomitant high-dose IV infusions of furosemide. The primary outcome was 48-h weight loss. RESULTS The cohort exhibited DR prior to enrollment, producing 1,188 +/- 476 ml of urine in 12 h during high-dose loop diuretic therapy (IV furosemide: 612 +/- 439 mg/day). All 3 interventions significantly improved diuretic efficacy (p < 0.001). Compared to metolazone (4.6 +/- 2.7 kg), neither IV chlorothiazide (5.8 +/- 2.7 kg; 1.2 kg [95% confidence interval (CI)]: -2.9 to 0.6; p = 0.292) nor tolvaptan (4.1 +/- 3.3 kg; 0.5 kg [95% CI: -1.5 to 2.4; p = 0.456) resulted in more weight loss at 48 h. Median (interquartile range [IQR]) cumulative urine output increased significantly and did not differ among those receiving metolazone (7.78 [IQR: 6.59 to 10.10] l) and chlorothiazide (8.77 [IQR: 7.37 to 10.86] l; p = 0.245) or tolvaptan (9.70 [IQR: 6.36 to 13.81] l; p = 0.160). Serum sodium decreased less with tolvaptan than with metolazone (+4 +/- 5 vs. -1 +/- 3 mEq/l; p = 0.001), but 48-h spot urine sodium was lower with tolvaptan (58 +/- 25 mmol/l) than with metolazone (104 +/- 16 mmol/l; p = 0.002) and with chlorothiazide (117 +/- 14 mmol/l; p < 0.001). CONCLUSIONS In this moderately sized DR trial, weight loss was excellent with the addition of metolazone, IV chlorothiazide, or tolvaptan to loop diuretics, without a detectable between-group difference. (C) 2020 by the American College of Cardiology Foundation.