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Dapagliflozin vs. metolazone in heart failure resistant to loop diuretics. 2023

Su Ern Yeoh, and Joanna Osmanska, and Mark C Petrie, and Katriona J M Brooksbank, and Andrew L Clark, and Kieran F Docherty, and Paul W X Foley, and Kaushik Guha, and Crawford A Halliday, and Pardeep S Jhund, and Paul R Kalra, and Gemma McKinley, and Ninian N Lang, and Matthew M Y Lee, and Alex McConnachie, and James J McDermott, and Elke Platz, and Peter Sartipy, and Alison Seed, and Bethany Stanley, and Robin A P Weir, and Paul Welsh, and John J V McMurray, and Ross T Campbell
BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.

To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide. A multi-centre, open-label, randomized, and active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 h). The primary endpoint was a diuretic effect, assessed by change in weight (kg). Secondary endpoints included a change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score. 61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 h was 977 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 h was 3.0 (2.5) kg with dapagliflozin compared to 3.6 (2.0) kg with metolazone [mean difference 0.65, 95% confidence interval (CI) -0.12,1.41 kg; P = 0.11]. Loop diuretic efficiency was less with dapagliflozin than with metolazone [mean 0.15 (0.12) vs. 0.25 (0.19); difference -0.08, 95% CI -0.17,0.01 kg; P = 0.10]. Changes in pulmonary congestion and volume assessment score were similar between treatments. Decreases in plasma sodium and potassium and increases in urea and creatinine were smaller with dapagliflozin than with metolazone. Serious adverse events were similar between treatments. In patients with heart failure and loop diuretic resistance, dapagliflozin was not more effective at relieving congestion than metolazone. Patients assigned to dapagliflozin received a larger cumulative dose of furosemide but experienced less biochemical upset than those assigned to metolazone. ClinicalTrials.gov Identifier: NCT04860011.

UI MeSH Term Description Entries
D008788 Metolazone A quinazoline-sulfonamide derived DIURETIC that functions by inhibiting SODIUM CHLORIDE SYMPORTERS. Diulo,Microx,Mykrox,SR-720-22,Zaroxolyn,SR 720 22,SR72022
D004232 Diuretics Agents that promote the excretion of urine through their effects on kidney function. Diuretic,Diuretic Effect,Diuretic Effects,Effect, Diuretic,Effects, Diuretic
D005665 Furosemide A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY. Frusemide,Fursemide,Errolon,Frusemid,Furanthril,Furantral,Furosemide Monohydrochloride,Furosemide Monosodium Salt,Fusid,Lasix
D006333 Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION. Cardiac Failure,Heart Decompensation,Congestive Heart Failure,Heart Failure, Congestive,Heart Failure, Left-Sided,Heart Failure, Right-Sided,Left-Sided Heart Failure,Myocardial Failure,Right-Sided Heart Failure,Decompensation, Heart,Heart Failure, Left Sided,Heart Failure, Right Sided,Left Sided Heart Failure,Right Sided Heart Failure
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012964 Sodium A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23
D049994 Sodium Potassium Chloride Symporter Inhibitors Agents that inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS which are concentrated in the thick ascending limb at the junction of the LOOP OF HENLE and KIDNEY TUBULES, DISTAL. They act as DIURETICS. Excess use is associated with HYPOKALEMIA and HYPERGLYCEMIA. Loop Diuretic,Bumetanide Sensitive Na-K-Cl-Transporter Inhibitors,High Ceiling Diuretics,Loop Diuretics,Na-K-CL Symporter Inhibitors,Sodium Potassium Chloride Cotransporter Inhibitors,Bumetanide Sensitive Na K Cl Transporter Inhibitors,Ceiling Diuretics, High,Diuretic, Loop,Diuretics, High Ceiling,Diuretics, Loop,Inhibitors, Na-K-CL Symporter,Na K CL Symporter Inhibitors,Symporter Inhibitors, Na-K-CL

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