{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T19:33:44Z","timestamp":1792870424518,"version":"4.5.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"44","license":[{"start":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T00:00:00Z","timestamp":1566172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Brazilian National Council for Scientific and Technological Development"},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Brazilian Research Network In Heart Failure","award":["467110\/2014-0"],"award-info":[{"award-number":["467110\/2014-0"]}]},{"name":"Brazilian Research Network In Heart Failure","award":["310679\/2016-8"],"award-info":[{"award-number":["310679\/2016-8"]}]},{"DOI":"10.13039\/501100004901","name":"FAPEMIG","doi-asserted-by":"publisher","award":["PPM-00428-17"],"award-info":[{"award-number":["PPM-00428-17"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"FAPEMIG","doi-asserted-by":"publisher","award":["30833\/2017-1"],"award-info":[{"award-number":["30833\/2017-1"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Although loop diuretics are widely used to treat heart failure (HF), there is scarce contemporary data to guide diuretic adjustments in the outpatient setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In a prospective, randomized and double-blind protocol, we tested the safety and tolerability of withdrawing low-dose furosemide in stable HF outpatients at 11 HF clinics in Brazil. The trial had two blindly adjudicated co-primary outcomes: (i) symptoms assessment quantified as the area under the curve (AUC) of a dyspnoea score on a visual-analogue scale evaluated at 4 time-points (baseline, Day 15, Day 45, and Day 90) and (ii) the proportion of patients maintained without diuretic reuse during follow-up. We enrolled 188 patients (25% females; 59\u2009\u00b1\u200913\u2009years old; left ventricular ejection fraction\u2009=\u200932\u2009\u00b1\u20098%) that were randomized to furosemide withdrawal (n\u2009=\u200995) or maintenance (n\u2009=\u200993). For the first co-primary endpoint, no significant difference in patients\u2019 assessment of dyspnoea was observed in the comparison of furosemide withdrawal with continuous administration [median AUC 1875 (interquartile range, IQR 383\u20133360) and 1541 (IQR 474\u20133124), respectively; P\u2009=\u20090.94]. For the second co-primary endpoint, 70 patients (75.3%) in the withdrawal group and 77 patients (83.7%) in the maintenance group were free of furosemide reuse during follow-up (odds ratio for additional furosemide use with withdrawal 1.69, 95% confidence interval 0.82\u20133.49; P\u2009=\u20090.16). Heart failure-related events (hospitalizations, emergency room visits, and deaths) were infrequent and similar between groups (P\u2009=\u20091.0).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Diuretic withdrawal did not result in neither increased self-perception of dyspnoea nor increased need of furosemide reuse. Diuretic discontinuation may deserve consideration in stable outpatients with no signs of fluid retention receiving optimal medical therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>ClinicalTrials.gov Identifier<\/jats:title>\n                    <jats:p>NCT02689180.<\/jats:p>\n                    <jats:p\/>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehz554","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T07:07:36Z","timestamp":1563952056000},"page":"3605-3612","source":"Crossref","is-referenced-by-count":81,"title":["Short-term diuretic withdrawal in stable outpatients with mild heart failure and no fluid retention receiving optimal therapy: a double-blind, multicentre, randomized trial"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6557-393X","authenticated-orcid":false,"given":"Luis E","family":"Rohde","sequence":"first","affiliation":[{"name":"Hospital de Cl\u00ednicas de Porto Alegre and Faculdade de Medicina da Universidade Federal do Rio Grande do Sul , Rua Ramiro Barcelos 2350, CEP, Porto Alegre, RS, Brazil"},{"name":"Hospital Moinhos de Vento, Rua Ramiro Barcelos 910, CEP , Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6048-8317","authenticated-orcid":false,"given":"Marciane M","family":"Rover","sequence":"additional","affiliation":[{"name":"Instituto de Cardiologia, Funda\u00e7\u00e3o Universit\u00e1ria de Cardiologia , Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A","family":"Figueiredo Neto","sequence":"additional","affiliation":[{"name":"Hospital Universit\u00e1rio da Universidade Federal do Maranh\u00e3o , S\u00e3o Luis, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz C","family":"Danzmann","sequence":"additional","affiliation":[{"name":"Hospital Universit\u00e1rio da Universidade Luterana do Brasil , Canoas, RS, Brazil"},{"name":"Hospital S\u00e3o Lucas da Pontif\u00edcia Universidade Cat\u00f3lica , Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7290-0348","authenticated-orcid":false,"given":"Eduardo G","family":"Bertoldi","sequence":"additional","affiliation":[{"name":"Hospital Escola da Universidade Federal de Pelotas , Pelotas, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus V","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Hospital das Cl\u00ednicas da Faculdade de Medicina de Ribeir\u00e3o Preto da Universidade de S\u00e3o Paulo , Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5538-7455","authenticated-orcid":false,"given":"Odilson M","family":"Silvestre","sequence":"additional","affiliation":[{"name":"Universidade Federal do Acre, Rio Branco , AC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio L P","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Hospital da Clinicas e Faculdade de Medicina da Universidade Federal de Minas Gerais , Belo Horizonte, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia Zytynski","family":"Moura","sequence":"additional","affiliation":[{"name":"Hospital Universit\u00e1rio Cajuru da Pontif\u00edcia Universidade Cat\u00f3lica , Curitiba, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5702-210X","authenticated-orcid":false,"given":"Luis","family":"Beck-da-Silva","sequence":"additional","affiliation":[{"name":"Hospital de Cl\u00ednicas de Porto Alegre and Faculdade de Medicina da Universidade Federal do Rio Grande do Sul , Rua Ramiro Barcelos 2350, CEP, Porto Alegre, RS, Brazil"},{"name":"Hospital Moinhos de Vento, Rua Ramiro Barcelos 910, CEP , Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7686-3353","authenticated-orcid":false,"given":"Debora","family":"Prado","sequence":"additional","affiliation":[{"name":"Hospital da Clinicas e Faculdade de Medicina da Universidade Federal de Minas Gerais , Belo Horizonte, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto T","family":"Sant'Anna","sequence":"additional","affiliation":[{"name":"Instituto de Cardiologia, Funda\u00e7\u00e3o Universit\u00e1ria de Cardiologia , Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo H","family":"Bridi","sequence":"additional","affiliation":[{"name":"Instituto de Cardiologia, Funda\u00e7\u00e3o Universit\u00e1ria de Cardiologia , Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Zimerman","sequence":"additional","affiliation":[{"name":"Hospital de Cl\u00ednicas de Porto Alegre and Faculdade de Medicina da Universidade Federal do Rio Grande do Sul , Rua Ramiro Barcelos 2350, CEP, Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila","family":"Raupp da Rosa","sequence":"additional","affiliation":[{"name":"Hospital S\u00e3o Lucas da Pontif\u00edcia Universidade Cat\u00f3lica , Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9ia","family":"Biolo","sequence":"additional","affiliation":[{"name":"Hospital de Cl\u00ednicas de Porto Alegre and Faculdade de Medicina da Universidade Federal do Rio Grande do Sul , Rua Ramiro Barcelos 2350, CEP, Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,19]]},"reference":[{"key":"2022102615083166700_ehz554-B1","first-page":"436","article-title":"Diretriz Brasileira de Insufici\u00eancia Card\u00edaca Cr\u00f4nica e Aguda","volume":"111","year":"2018","journal-title":"Arq Bras Cardiol"},{"key":"2022102615083166700_ehz554-B2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000164149","article-title":"Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry","volume":"113","author":"Peacock","year":"2009","journal-title":"Cardiology"},{"key":"2022102615083166700_ehz554-B3","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/S0195-668X(02)00700-5","article-title":"Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology. The Euro Heart Failure Survey programme\u2014a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment","volume":"24","author":"Komajda","year":"2003","journal-title":"Eur Heart J"},{"key":"2022102615083166700_ehz554-B4","first-page":"433","article-title":". I Brazilian Registry of Heart Failure\u2014clinical aspects, care quality and hospitalization outcomes","volume":"104","author":"Albuquerque","year":"2015","journal-title":"Arq Bras Cardiol"},{"key":"2022102615083166700_ehz554-B5","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/j.amjcard.2005.12.072","article-title":"Relation of loop diuretic dose to mortality in advanced heart failure","volume":"97","author":"Eshaghian","year":"2006","journal-title":"Am J Cardiol"},{"key":"2022102615083166700_ehz554-B6","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1111\/ijcp.12144","article-title":"Effects on survival of loop diuretic dosing in ambulatory patients with chronic heart failure using a propensity score analysis","volume":"67","author":"Dini","year":"2013","journal-title":"Int J Clin Pract"},{"key":"2022102615083166700_ehz554-B7","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/S0140-6736(86)90298-9","article-title":"Symptomatic assessment of patients with heart failure: double blind comparison of increasing doses of diuretics and captopril in moderate heart failure","volume":"2","author":"Cowley","year":"1986","journal-title":"Lancet"},{"key":"2022102615083166700_ehz554-B8","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(87)91074-9","article-title":"Double blind comparison of captopril alone against frusemide pus amiloride in mild heart failure","volume":"2","author":"Richardson","year":"1987","journal-title":"Lancet"},{"key":"2022102615083166700_ehz554-B9","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Associations (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur Heart J"},{"key":"2022102615083166700_ehz554-B10","first-page":"e240","article-title":"2013 ACCF\/AHA Guideline for the Management of Heart Failure. A report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines","volume":"128","author":"Yancy","year":"2013","journal-title":"Circulation"},{"key":"2022102615083166700_ehz554-B11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ahj.2017.08.012","article-title":"Rational and design of a randomized, double-blind, multicenter trial to evaluate the safety and tolerability of furosemide withdrawal in stable chronic outpatients with heart failure: the ReBIC-1 trial","volume":"194","author":"da Rosa","year":"2017","journal-title":"Am Heart J"},{"key":"2022102615083166700_ehz554-B12","first-page":"697","article-title":"Reliability and prognostic value of traditional signs and symptoms in outpatients with congestive heart failure","volume":"20","author":"Rohde","year":"2004","journal-title":"Can J Cardiol"},{"key":"2022102615083166700_ehz554-B13","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1111\/j.1365-2702.2010.03403.x","article-title":"Nurses' performance in classifying heart failure patients based on physical exam: comparison with cardiologist's physical exam and levels of N-terminal pro-B-type natriuretic peptide","volume":"19","author":"Sauer","year":"2010","journal-title":"J Clin Nurs"},{"key":"2022102615083166700_ehz554-B14","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":"2022102615083166700_ehz554-B15","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1136\/bmj.315.7106.464","article-title":"Withdrawal of long term diuretic medication in elderly patients: a double blind randomised trial","volume":"315","author":"Walma","year":"1997","journal-title":"BMJ"},{"key":"2022102615083166700_ehz554-B16","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.ijcard.2014.09.156","article-title":"Lowering furosemide dose in stable chronic heart failure patients with reduced ejection fraction is not accompanied by decompensation: a randomized study","volume":"177","author":"Kapelios","year":"2014","journal-title":"Int J Cardiol"},{"key":"2022102615083166700_ehz554-B17","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S0735-1097(03)00765-4","article-title":"Diuretic use, progressive heart failure, and death in patients in the Studies Of Left Ventricular Dysfunction (SOLVD)","volume":"42","author":"Domanski","year":"2003","journal-title":"J Am Coll Cardiol"},{"key":"2022102615083166700_ehz554-B18","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s10557-016-6697-7","article-title":"Cardiac dysfunction, congestion and loop diuretics: their relationship to prognosis in heart failure","volume":"30","author":"Pellicori","year":"2016","journal-title":"Cardiovasc Drugs Ther"},{"key":"2022102615083166700_ehz554-B19","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.cardfail.2017.04.001","article-title":"Prognostic effect of the dose of loop diuretic over 5 years in chronic heart failure","volume":"23","author":"Laszczy\u0144ska","year":"2017","journal-title":"J Card Fail"},{"key":"2022102615083166700_ehz554-B20","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.jchf.2014.05.014","article-title":"The effects of dose reduction of furosemide on glomerular filtration rate in stable systolic heart failure","volume":"2","author":"Mckie","year":"2014","journal-title":"JACC Heart Fail"},{"key":"2022102615083166700_ehz554-B21","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0140-6736(18)32484-X","article-title":"Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial","volume":"393","author":"Halliday","year":"2019","journal-title":"Lancet"},{"key":"2022102615083166700_ehz554-B22","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1002\/ejhf.748","article-title":"The effects of short-term omission of daily medication on the pathophysiology of heart failure","volume":"19","author":"Dovancescu","year":"2017","journal-title":"Eur J Heart Fail"}],"container-title":["European Heart Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurheartj\/article-pdf\/40\/44\/3605\/46646135\/eurheartj_40_44_3605.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurheartj\/article-pdf\/40\/44\/3605\/46646135\/eurheartj_40_44_3605.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T11:42:16Z","timestamp":1666784536000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurheartj\/article\/40\/44\/3605\/5551388"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,19]]},"references-count":22,"journal-issue":{"issue":"44","published-online":{"date-parts":[[2019,8,19]]},"published-print":{"date-parts":[[2019,11,21]]}},"URL":"https:\/\/doi.org\/10.1093\/eurheartj\/ehz554","relation":{},"ISSN":["0195-668X","1522-9645"],"issn-type":[{"value":"0195-668X","type":"print"},{"value":"1522-9645","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,11,21]]},"published":{"date-parts":[[2019,8,19]]}}}