{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T19:33:45Z","timestamp":1792870425303,"version":"4.5.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"31","license":[{"start":{"date-parts":[[2023,5,21]],"date-time":"2023-05-21T00:00:00Z","timestamp":1684627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>A multi-centre, open-label, randomized, and active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5\u201310 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 (\u00b1standard deviation) cumulative dose of furosemide at 96 h was 977 (\u00b1492) mg in the dapagliflozin group and 704 (\u00b1428) mg in patients assigned to metolazone. The mean (\u00b1standard 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) \u22120.12,1.41 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 \u22120.08, 95% CI \u22120.17,0.01 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration<\/jats:title>\n                  <jats:p>ClinicalTrials.gov Identifier: NCT04860011<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehad341","type":"journal-article","created":{"date-parts":[[2023,5,21]],"date-time":"2023-05-21T18:12:46Z","timestamp":1684692766000},"page":"2966-2977","source":"Crossref","is-referenced-by-count":106,"title":["Dapagliflozin vs. metolazone in heart failure resistant to loop diuretics"],"prefix":"10.1093","volume":"44","author":[{"given":"Su Ern","family":"Yeoh","sequence":"first","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Osmanska","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-9496","authenticated-orcid":false,"given":"Mark C","family":"Petrie","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9129-1717","authenticated-orcid":false,"given":"Katriona J M","family":"Brooksbank","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8362-668X","authenticated-orcid":false,"given":"Andrew L","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hull University Teaching Hospitals NHS Trust, Castle Hill Hospital , Cottingham HU3 2JZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5446-9969","authenticated-orcid":false,"given":"Kieran F","family":"Docherty","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4856-832X","authenticated-orcid":false,"given":"Paul W X","family":"Foley","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Great Western Hospital , Swindon SN3 6BB , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaushik","family":"Guha","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Portsmouth Hospitals University NHS Trust , Portsmouth PO6 3LY , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crawford A","family":"Halliday","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Royal Alexandria Hospital, NHS Greater Glasgow and Clyde , Paisley , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4306-5317","authenticated-orcid":false,"given":"Pardeep S","family":"Jhund","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R","family":"Kalra","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Portsmouth Hospitals University NHS Trust , Portsmouth PO6 3LY , UK"},{"name":"Faculty of Science and Health, University of Portsmouth , Portsmouth PO1 2DT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"McKinley","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, School of Health and Wellbeing, University of Glasgow , Glasgow G12 8TB , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8441-6887","authenticated-orcid":false,"given":"Ninian N","family":"Lang","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9213-2067","authenticated-orcid":false,"given":"Matthew M Y","family":"Lee","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7262-7000","authenticated-orcid":false,"given":"Alex","family":"McConnachie","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, School of Health and Wellbeing, University of Glasgow , Glasgow G12 8TB , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J","family":"McDermott","sequence":"additional","affiliation":[{"name":"Biopharmaceuticals, Medical Affairs, AstraZeneca , Wilmington, DE 19803 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-0710","authenticated-orcid":false,"given":"Elke","family":"Platz","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sartipy","sequence":"additional","affiliation":[{"name":"Cardiovascular, Renal and Metabolism, AstraZeneca, BioPharmaceuticals R&D , Gothenburg 431 83 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Seed","sequence":"additional","affiliation":[{"name":"Lancashire Cardiac Centre, Blackpool Teaching Hospitals NHS Trust , Blackpool FY3 8NP , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3299-4014","authenticated-orcid":false,"given":"Bethany","family":"Stanley","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, School of Health and Wellbeing, University of Glasgow , Glasgow G12 8TB , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9895-2795","authenticated-orcid":false,"given":"Robin A P","family":"Weir","sequence":"additional","affiliation":[{"name":"Cardiology Department, University Hospital Hairmyres , Lanarkshire G75 8RG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-3643","authenticated-orcid":false,"given":"Paul","family":"Welsh","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-3975","authenticated-orcid":false,"given":"John J V","family":"McMurray","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-2129","authenticated-orcid":false,"given":"Ross T","family":"Campbell","sequence":"additional","affiliation":[{"name":"BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow , 126 University Place, Glasgow G12 8TA , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,21]]},"reference":[{"key":"2023081417245977200_ehad341-B1","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1161\/HYPERTENSIONAHA.120.15205","article-title":"Pathophysiology of diuretic resistance and its implications for the management of chronic heart failure","volume":"76","author":"Wilcox","year":"2020","journal-title":"Hypertension"},{"key":"2023081417245977200_ehad341-B2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1053\/j.ajkd.2016.08.027","article-title":"Diuretic resistance","volume":"69","author":"Hoorn","year":"2017","journal-title":"Am J Kidney Dis"},{"key":"2023081417245977200_ehad341-B3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s10741-019-09851-9","article-title":"Loop diuretic resistance complicating acute heart failure","volume":"25","author":"Cox","year":"2020","journal-title":"Heart Fail Rev"},{"key":"2023081417245977200_ehad341-B4","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.jacc.2019.12.059","article-title":"Diuretic therapy for patients with heart failure: JACC state-of-the-art review","volume":"75","author":"Felker","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"2023081417245977200_ehad341-B5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11897-019-0424-1","article-title":"Diuretic resistance in heart failure","volume":"16","author":"Gupta","year":"2019","journal-title":"Curr Heart Fail Rep"},{"key":"2023081417245977200_ehad341-B6","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nrcardio.2014.215","article-title":"Diuretic response in acute heart failure-pathophysiology, evaluation, and therapy","volume":"12","author":"ter Maaten","year":"2015","journal-title":"Nat Rev Cardiol"},{"key":"2023081417245977200_ehad341-B7","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ejhf.1369","article-title":"The use of diuretics in heart failure with congestion - a position statement from the heart failure association of the European society of cardiology","volume":"21","author":"Mullens","year":"2019","journal-title":"Eur J Heart Fail"},{"key":"2023081417245977200_ehad341-B8","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur Heart J"},{"key":"2023081417245977200_ehad341-B9","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1056\/NEJMoa1210357","article-title":"Ultrafiltration in decompensated heart failure with cardiorenal syndrome","volume":"367","author":"Bart","year":"2012","journal-title":"N Engl J Med"},{"key":"2023081417245977200_ehad341-B10","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.jacc.2006.07.073","article-title":"Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure","volume":"49","author":"Costanzo","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"2023081417245977200_ehad341-B11","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1056\/NEJMoa1005419","article-title":"Diuretic strategies in patients with acute decompensated heart failure","volume":"364","author":"Felker","year":"2011","journal-title":"N Engl J Med"},{"key":"2023081417245977200_ehad341-B12","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1001\/jama.2013.282190","article-title":"Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial","volume":"310","author":"Chen","year":"2013","journal-title":"JAMA"},{"key":"2023081417245977200_ehad341-B13","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/eurheartj\/ehac689","article-title":"Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial","volume":"44","author":"Trullas","year":"2023","journal-title":"Eur Heart J"},{"key":"2023081417245977200_ehad341-B14","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.jchf.2019.09.012","article-title":"Diuretic strategies for loop diuretic resistance in acute heart failure: the 3T trial","volume":"8","author":"Cox","year":"2020","journal-title":"JACC Heart Fail"},{"key":"2023081417245977200_ehad341-B15","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1001\/jama.297.12.1319","article-title":"Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST outcome trial","volume":"297","author":"Konstam","year":"2007","journal-title":"JAMA"},{"key":"2023081417245977200_ehad341-B16","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/j.jacc.2016.12.035","article-title":"Short-Term effects of tolvaptan in patients with acute heart failure and volume overload","volume":"69","author":"Konstam","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"2023081417245977200_ehad341-B17","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1056\/NEJMoa2203094","article-title":"Acetazolamide In acute decompensated heart failure with volume overload","volume":"387","author":"Mullens","year":"2022","journal-title":"N Engl J Med"},{"key":"2023081417245977200_ehad341-B18","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.cjca.2019.01.022","article-title":"Spironolactone in acute heart failure patients with renal dysfunction and risk factors for diuretic resistance: from the ATHENA-HF trial","volume":"35","author":"Greene","year":"2019","journal-title":"Can J Cardiol"},{"key":"2023081417245977200_ehad341-B19","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1002\/ejhf.2384","article-title":"Worsening renal function in acute heart failure in the context of diuretic response","volume":"24","author":"Emmens","year":"2022","journal-title":"Eur J Heart Fail"},{"key":"2023081417245977200_ehad341-B20","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1161\/CIRCHEARTFAILURE.111.963413","article-title":"Is worsening renal function an ominous prognostic sign in patients with acute heart failure? The role of congestion and its interaction with renal function","volume":"5","author":"Metra","year":"2012","journal-title":"Circ Heart Fail"},{"key":"2023081417245977200_ehad341-B21","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1007\/s00424-014-1619-7","article-title":"Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart","volume":"467","author":"Vrhovac","year":"2015","journal-title":"Pflugers Arch"},{"key":"2023081417245977200_ehad341-B22","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1161\/HYPERTENSIONAHA.119.11684","article-title":"Antihypertensive and renal mechanisms of SGLT2 (sodium-glucose linked transporter 2) inhibitors","volume":"75","author":"Wilcox","year":"2020","journal-title":"Hypertension"},{"key":"2023081417245977200_ehad341-B23","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/dom.13126","article-title":"Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis","volume":"20","author":"Hallow","year":"2018","journal-title":"Diabetes Obes Metab"},{"key":"2023081417245977200_ehad341-B24","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S0140-6736(22)01429-5","article-title":"SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials","volume":"400","author":"Vaduganathan","year":"2022","journal-title":"Lancet"},{"key":"2023081417245977200_ehad341-B25","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.jchf.2019.07.008","article-title":"Lung ultrasound in acute heart failure: prevalence of pulmonary congestion and short- and long-term outcomes","volume":"7","author":"Platz","year":"2019","journal-title":"JACC Heart Fail"},{"key":"2023081417245977200_ehad341-B26","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1177\/2048872620901835","article-title":"Quantification of pleural effusions on thoracic ultrasound in acute heart failure","volume":"9","author":"Lindner","year":"2020","journal-title":"Eur Heart J Acute Cardiovasc Care"},{"key":"2023081417245977200_ehad341-B27","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/ejhf.1713","article-title":"Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF)","volume":"22","author":"Damman","year":"2020","journal-title":"Eur J Heart Fail"},{"key":"2023081417245977200_ehad341-B28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/eurheartj\/ehac530","article-title":"Impact of empagliflozin on decongestion in acute heart failure: the EMPULSE trial","volume":"44","author":"Biegus","year":"2023","journal-title":"Eur Heart J"},{"key":"2023081417245977200_ehad341-B29","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1161\/CIRCULATIONAHA.122.062486","article-title":"Decongestion with Acetazolamide in acute decompensated heart failure across the Spectrum of left ventricular ejection fraction: a prespecified analysis from the ADVOR trial","volume":"147","author":"Martens","year":"2023","journal-title":"Circulation"},{"key":"2023081417245977200_ehad341-B30","doi-asserted-by":"crossref","DOI":"10.1002\/ejhf.2863","article-title":"Sodium and potassium changes during decongestion with Acetazolamide\u2014a prespecified analysis from the ADVOR trial","author":"Dhont","year":"2023","journal-title":"Eur J Heart Fail"}],"container-title":["European Heart Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurheartj\/advance-article-pdf\/doi\/10.1093\/eurheartj\/ehad341\/50396917\/ehad341.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurheartj\/article-pdf\/44\/31\/2966\/51111069\/ehad341.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurheartj\/article-pdf\/44\/31\/2966\/51111069\/ehad341.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T17:25:26Z","timestamp":1692033926000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurheartj\/article\/44\/31\/2966\/7173307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,21]]},"references-count":30,"journal-issue":{"issue":"31","published-online":{"date-parts":[[2023,5,21]]},"published-print":{"date-parts":[[2023,8,14]]}},"URL":"https:\/\/doi.org\/10.1093\/eurheartj\/ehad341","relation":{},"ISSN":["0195-668X","1522-9645"],"issn-type":[{"value":"0195-668X","type":"print"},{"value":"1522-9645","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,8,14]]},"published":{"date-parts":[[2023,5,21]]}}}