{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T15:36:05Z","timestamp":1793806565070,"version":"4.6.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council Clinician Scientist","award":["MR\/X001881\/1"],"award-info":[{"award-number":["MR\/X001881\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Several diuretic strategies, including furosemide i.v. boluses (FB) or continuous infusion (FC), are used in acute heart failure (AHF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We systematically searched phase 3 randomized clinical trials (RCTs) evaluating diuretic regimens in admitted AHF patients within 48\u2005h and irrespective of clinical stabilization. We calculated the odds ratio (OR) of FC or FB plus another diuretic (sequential nephron blockade, SNB) compared to FB alone on 24\u2005h weight loss (WL) and worsening renal function (WRF), with a random-effects model with inverse variance weighting. Urine output, hypokalaemia, hyponatremia, and all-cause mortality\/rehospitalization were secondary endpoints. In 25 selected RCTs (7149 patients, mean age 68.9 \u00b1 8.7 years, mean left ventricular ejection fraction 38.2 \u00b1 10.7%), FC [OR 1.55 (95% confidence interval 1.39\u20131.63)], FB plus tolvaptan [OR 1.57 (1.39\u20131.77)], FB plus SGLT2i [OR 1.23 (1.06\u20131.42)], and FB plus thiazide [OR 1.63 (1.37\u20131.94)] were associated with greater WL than FB. FB plus SGLT2i [OR 1.52 (1.19\u20131.94)] and FB plus acetazolamide [OR 1.81 (1.31\u20132.49)] were associated with WRF. FB plus thiazide was associated with both WRF [OR 1.78 (1.43\u20132.21)] and hypokalaemia [OR 1.69 (1.32\u20132.16)]. Results were consistent in sensitivity analyses considering urine output, RCTs protocol-established furosemide doses, or daily furosemide dose. Congestion\/decongestion scores and clinical outcomes were reported in around 50% of RCTs. In an underpowered exploratory analysis, mortality\/rehospitalization was non-significantly lower with SGLT2i [OR 0.45 (0.19\u20131.07)].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>FC and SNB improve surrogates of response to FB in AHF. SNB is also connoted by WRF and may induce hypokalaemia. The endpoints of diuretic RCTs should be revised and harmonized.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjcvp\/pvaf067","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T11:31:16Z","timestamp":1757417476000},"page":"6-14","source":"Crossref","is-referenced-by-count":7,"title":["Diuretic strategies in acute heart failure: a systematic review and network meta-analysis of randomized clinical trials"],"prefix":"10.1093","volume":"12","author":[{"given":"Antonio","family":"Cannat\u00e0","sequence":"first","affiliation":[{"name":"School of Cardiovascular Medicine & Sciences, King\u2019s College London British Heart Foundation Centre of Excellence , London ,","place":["UK"]},{"name":"King\u2019s College Hospital NHS Foundation Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Anastasia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genova , Genova ,","place":["Italy"]},{"name":"Cardiology Department, Casa di Cura Villa Verde , Taranto ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"De Marzo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genova , Genova ,","place":["Italy"]},{"name":"Cardiology Department, IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oren","family":"Caspi","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, Cardiology Department, Rambam Health Care Campus and The Bruce and Ruth Rapport Faculty of Medicine, Technion\u2014Israel Institute of Technology , Haifa ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bromage","sequence":"additional","affiliation":[{"name":"School of Cardiovascular Medicine & Sciences, King\u2019s College London British Heart Foundation Centre of Excellence , London ,","place":["UK"]},{"name":"King\u2019s College Hospital NHS Foundation Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9854-5046","authenticated-orcid":false,"given":"Italo","family":"Porto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genova , Genova ,","place":["Italy"]},{"name":"Cardiac, Thoracic and Vascular Department, IRCCS Ospedale Policlinico San Martino , Genova ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7732-0887","authenticated-orcid":false,"given":"Gianluigi","family":"Savarese","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset; Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"McDonagh","sequence":"additional","affiliation":[{"name":"School of Cardiovascular Medicine & Sciences, King\u2019s College London British Heart Foundation Centre of Excellence , London ,","place":["UK"]},{"name":"King\u2019s College Hospital NHS Foundation Trust , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary L","family":"Cox","sequence":"additional","affiliation":[{"name":"Lipscomb University College of Pharmacy , Nashville, TN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7167-7287","authenticated-orcid":false,"given":"Pietro","family":"Ameri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genova , Genova ,","place":["Italy"]},{"name":"Cardiac, Thoracic and Vascular Department, IRCCS Ospedale Policlinico San Martino , Genova ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"2026020209254924700_pvaf067-B1","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.jacc.2019.12.059","article-title":"Diuretic therapy for patients with heart failure","volume":"75","author":"Felker","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"2026020209254924700_pvaf067-B2","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1002\/ejhf.2634","article-title":"Combination diuretic therapy for acute heart failure: \u2018alone we can do so little; together we can do so much.\u2019","volume":"24","author":"Bromage","year":"2022","journal-title":"Eur J Heart Fail"},{"key":"2026020209254924700_pvaf067-B3","first-page":"l4898","article-title":"Rob 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ (Clin Res Ed)"},{"key":"2026020209254924700_pvaf067-B4","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":"2026020209254924700_pvaf067-B5","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00392-019-01521-y","article-title":"Diuretic treatment in high-risk acute decompensation of advanced chronic heart failure\u2014bolus intermittent vs. continuous infusion of furosemide: a randomized controlled trial","volume":"109","author":"Frea","year":"2020","journal-title":"Clin Res Cardiol"},{"key":"2026020209254924700_pvaf067-B6","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1016\/j.amjcard.2010.01.355","article-title":"Continuous versus bolus dosing of furosemide for patients hospitalized for heart failure","volume":"105","author":"Allen","year":"2010","journal-title":"Am J Cardiol"},{"key":"2026020209254924700_pvaf067-B7","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1136\/emermed-2013-202526","article-title":"Clinical effects and safety of different strategies for administering intravenous diuretics in acutely decompensated heart failure: a randomised clinical trial","volume":"31","author":"Llorens","year":"2014","journal-title":"Emerg Med J"},{"key":"2026020209254924700_pvaf067-B8","doi-asserted-by":"crossref","first-page":"R134","DOI":"10.1186\/cc13952","article-title":"Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial","volume":"18","author":"Palazzuoli","year":"2014","journal-title":"Crit Care"},{"key":"2026020209254924700_pvaf067-B9","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.cardfail.2009.11.005","article-title":"Continuous versus intermittent infusion of furosemide in acute decompensated heart failure","volume":"16","author":"Thomson","year":"2010","journal-title":"J Card Fail"},{"key":"2026020209254924700_pvaf067-B10","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s00059-015-4327-y","article-title":"Comparison of three diuretic treatment strategies for patients with acute decompensated heart failure","volume":"40","author":"Yayla","year":"2015","journal-title":"Herz"},{"key":"2026020209254924700_pvaf067-B11","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1002\/ehf2.13286","article-title":"Continuous versus intermittent use of furosemide in patients with heart failure and moderate chronic renal dysfunction","volume":"8","author":"Zheng","year":"2021","journal-title":"ESC Heart Fail"},{"key":"2026020209254924700_pvaf067-B12","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ihj.2014.03.006","article-title":"A prospective, randomized study to evaluate the efficacy of various diuretic strategies in acute decompensated heart failure","volume":"66","author":"Shah","year":"2014","journal-title":"Indian Heart J"},{"key":"2026020209254924700_pvaf067-B13","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3109\/tcic.8.6.273.276","article-title":"Frusemide in pulmonary oedema: continuous versus intermittent","volume":"8","author":"Makhoul","year":"1997","journal-title":"Clin Intensive Care"},{"key":"2026020209254924700_pvaf067-B14","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":"2026020209254924700_pvaf067-B15","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":"Trull\u00e0s","year":"2023","journal-title":"Eur Heart J"},{"key":"2026020209254924700_pvaf067-B16","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":"2026020209254924700_pvaf067-B17","doi-asserted-by":"crossref","first-page":"16474","DOI":"10.1038\/s41598-021-96002-6","article-title":"Effect of adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure: a randomized clinical trial","volume":"11","author":"Piardi","year":"2021","journal-title":"Sci Rep"},{"key":"2026020209254924700_pvaf067-B18","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/j.jacc.2016.09.004","article-title":"Efficacy and safety of tolvaptan in patients hospitalized with acute heart failure","volume":"69","author":"Felker","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"2026020209254924700_pvaf067-B19","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1001\/jama.291.16.1963","article-title":"Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial","volume":"291","author":"Gheorghiade","year":"2004","journal-title":"JAMA"},{"key":"2026020209254924700_pvaf067-B20","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":"2026020209254924700_pvaf067-B21","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1253\/circj.CJ-16-1122","article-title":"Tolvaptan reduces the risk of worsening renal function in patients with acute decompensated heart failure and preserved left ventricular ejection fraction\u2015prospective randomized controlled study","volume":"81","author":"Tamaki","year":"2017","journal-title":"Circ J"},{"key":"2026020209254924700_pvaf067-B22","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1002\/ehf2.12783","article-title":"Tolvaptan vs. furosemide-based diuretic regimens in patients hospitalized for heart failure with hyponatremia (AQUA-AHF)","volume":"7","author":"Ng","year":"2020","journal-title":"ESC Heart Fail"},{"key":"2026020209254924700_pvaf067-B23","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.cardfail.2016.02.007","article-title":"Clinical effectiveness of tolvaptan in patients with acute heart failure and renal dysfunction","volume":"22","author":"Matsue","year":"2016","journal-title":"J Card Fail"},{"key":"2026020209254924700_pvaf067-B24","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1161\/CIRCULATIONAHA.122.059038","article-title":"Effects of early empagliflozin initiation on diuresis and kidney function in patients with acute decompensated heart failure (EMPAG-HF)","volume":"146","author":"Schulze","year":"2022","journal-title":"Circulation"},{"key":"2026020209254924700_pvaf067-B25","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.jacc.2024.02.009","article-title":"Efficacy and safety of dapagliflozin in patients with acute heart failure","volume":"83","author":"Cox","year":"2024","journal-title":"J Am Coll Cardiol"},{"key":"2026020209254924700_pvaf067-B26","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1136\/hrt.71.2.146","article-title":"Combination diuretic treatment in severe heart failure: a randomised controlled trial","volume":"71","author":"Channer","year":"1994","journal-title":"Heart"},{"key":"2026020209254924700_pvaf067-B27","doi-asserted-by":"crossref","first-page":"2966","DOI":"10.1093\/eurheartj\/ehad341","article-title":"Dapagliflozin vs. metolazone in heart failure resistant to loop diuretics","volume":"44","author":"Yeoh","year":"2023","journal-title":"Eur Heart J"},{"key":"2026020209254924700_pvaf067-B28","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.1093\/eurheartj\/ehad557","article-title":"Renal function and decongestion with acetazolamide in acute decompensated heart failure: the ADVOR trial","volume":"44","author":"Meekers","year":"2023","journal-title":"Eur Heart J"},{"key":"2026020209254924700_pvaf067-B29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jcrc.2013.10.009","article-title":"Loop diuretic strategies in patients with acute decompensated heart failure: a meta-analysis of randomized controlled trials","volume":"29","author":"Wu","year":"2014","journal-title":"J Crit Care"},{"key":"2026020209254924700_pvaf067-B30","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/S0735-1097(21)01975-6","article-title":"Continuous infusion versus intermittent bolus furosemide for acute decompensated heart failure: a systematic review and meta-analysis","volume":"77","author":"Shastri","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"2026020209254924700_pvaf067-B31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10741-018-9727-7","article-title":"Continuous versus intermittent administration of furosemide in acute decompensated heart failure: a systematic review and meta-analysis","volume":"24","author":"Kuriyama","year":"2019","journal-title":"Heart Fail Rev"},{"key":"2026020209254924700_pvaf067-B32","first-page":"CD014811","article-title":"Continuous infusion versus bolus injection of loop diuretics for acute heart failure","volume":"5","author":"Rasoul","year":"2024","journal-title":"Cochrane Database Syst Rev"},{"key":"2026020209254924700_pvaf067-B33","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ejhf.1369","article-title":"The use of diuretics in heart failure with congestion\u2014a 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":"2026020209254924700_pvaf067-B34","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1038\/s41591-023-02532-z","article-title":"Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial","volume":"29","author":"ter Maaten","year":"2023","journal-title":"Nat Med"},{"key":"2026020209254924700_pvaf067-B35","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1002\/ejhf.3632","article-title":"Urinary sodium analysis: the key to effective diuretic titration? European Journal of Heart Failure expert consensus document","volume":"27","author":"Meekers","year":"2025","journal-title":"Eur J Heart Fail"},{"key":"2026020209254924700_pvaf067-B36","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1001\/jama.297.12.1332","article-title":"Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST clinical status trials","volume":"297","author":"Gheorghiade","year":"2007","journal-title":"JAMA"},{"key":"2026020209254924700_pvaf067-B37","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":"2026020209254924700_pvaf067-B38","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ejheart.2008.01.011","article-title":"Worsening renal function in patients hospitalised for acute heart failure: clinical implications and prognostic significance","volume":"10","author":"Metra","year":"2008","journal-title":"Eur J Heart Fail"},{"key":"2026020209254924700_pvaf067-B39","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1161\/CIRCULATIONAHA.117.030112","article-title":"Worsening renal function in patients with acute heart failure undergoing aggressive diuresis is not associated with tubular injury","volume":"137","author":"Ahmad","year":"2018","journal-title":"Circulation"},{"key":"2026020209254924700_pvaf067-B40","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/s41591-021-01659-1","article-title":"The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial","volume":"28","author":"Voors","year":"2022","journal-title":"Nat Med"},{"key":"2026020209254924700_pvaf067-B41","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1001\/jama.2022.23924","article-title":"Effect of torsemide vs furosemide after discharge on all-cause mortality in patients hospitalized with heart failure","volume":"329","author":"Mentz","year":"2023","journal-title":"JAMA"},{"key":"2026020209254924700_pvaf067-B42","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1001\/jamacardio.2017.2198","article-title":"Efficacy and safety of spironolactone in acute heart failure: the ATHENA-HF randomized clinical trial","volume":"2","author":"Butler","year":"2017","journal-title":"JAMA Cardiol"}],"container-title":["European Heart Journal - Cardiovascular Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ehjcvp\/advance-article-pdf\/doi\/10.1093\/ehjcvp\/pvaf067\/64237398\/pvaf067.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article-pdf\/12\/1\/6\/64237398\/pvaf067.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article-pdf\/12\/1\/6\/64237398\/pvaf067.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:36:29Z","timestamp":1770042989000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article\/12\/1\/6\/8250742"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,10]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,9,10]]},"published-print":{"date-parts":[[2026,2,2]]}},"URL":"https:\/\/doi.org\/10.1093\/ehjcvp\/pvaf067","relation":{},"ISSN":["2055-6837","2055-6845"],"issn-type":[{"value":"2055-6837","type":"print"},{"value":"2055-6845","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,9,10]]}}}