Dapagliflozin versus metolazone in heart failure resistant to loop diuretics

Yeoh, S. E. et al. (2023) Dapagliflozin versus metolazone in heart failure resistant to loop diuretics. European Heart Journal, 44(31), pp. 2966-2977. (doi: 10.1093/eurheartj/ehad341) (PMID:37210742)

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Background and Aims: 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. Methods: A multi-centre, open-label, randomized, 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 hours). The primary endpoint was diuretic effect, assessed by change in weight (kg). Secondary endpoints included change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score. Results: 61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 hours was 976 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 hours 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) versus 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. Conclusion: 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.

Item Type:Articles
Additional Information:The DAPA-RESIST trial was funded by an investigator-initiated grant from AstraZeneca. J.J.V.M. is supported by a Centre of Research Excellence Grant from the British Heart Foundation (RE/18/6/34217).
Glasgow Author(s) Enlighten ID:Stanley, Miss Bethany and McConnachie, Professor Alex and Lee, Matthew and Docherty, Dr Kieran and Welsh, Professor Paul and Petrie, Professor Mark and McKinley, Miss Gemma and Osmanska, Dr Joanna and Campbell, Dr Ross and McMurray, Professor John and Brooksbank, Dr Katriona and Halliday, Dr Crawford and Jhund, Professor Pardeep and Kalra, Professor Paul and Lang, Professor Ninian and Yeoh, Dr Su
Authors: Yeoh, S. E., Osmanska, J., Petrie, M. C., Brooksbank, K. J.M., Clark, A. L., Docherty, K. F., Foley, P. W.X., Guha, K., Halliday, C. A., Jhund, P. S., Kalra, P. R., McKinley, G., Lang, N. N., Lee, M. M.Y., McConnachie, A., McDermott, J. J., Platz, E., Sartipy, P., Seed, A., Stanley, B., Weir, R. A.P., Welsh, P., McMurray, J. J.V., and Campbell, R. T.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name:European Heart Journal
Publisher:Oxford University Press
ISSN (Online):1522-9645
Published Online:21 May 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in European Heart Journal 44(31):2966-2977
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217SCMH - Cardiovascular & Metabolic Health