Dapagliflozin versus metolazone in heart failure resistant to loop diuretics (original) (raw)

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)

Abstract

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).
Status: Published
Refereed: Yes
Glasgow Author(s) Enlighten ID: Petrie, Professor Mark and Jhund, Professor Pardeep and Yeoh, Dr Su and McKinley, Miss Gemma and Brooksbank, Dr Katriona and Stanley, Miss Bethany and Osmanska, Dr Joanna and McMurray, Professor John and Campbell, Dr Ross and Docherty, Dr Kieran and Lee, Dr Matthew and Halliday, Dr Crawford and Lang, Professor Ninian and Welsh, Professor Paul and Kalra, Professor Paul and McConnachie, Professor Alex
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 HealthCollege of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name: European Heart Journal
Publisher: Oxford University Press
ISSN: 0195-668X
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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Funder and Project Information

BHF Centre of Excellence

Colin Berry

RE/18/6/34217

SCMH - Cardiovascular & Metabolic Health

Deposit and Record Details

ID Code: 298576
Depositing User: Ms Jacqui Brannan
Datestamp: 30 May 2023 11:28
Last Modified: 02 May 2025 07:31
Date of acceptance: 16 May 2023
Date of first online publication: 21 May 2023
Date Deposited: 18 May 2023