{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:21:48Z","timestamp":1787170908410,"version":"build-2736575974"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T00:00:00Z","timestamp":1580342400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T00:00:00Z","timestamp":1580342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Res Cardiol"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Loop diuretics are frequently prescribed to patients with heart failure and reduced ejection fraction (HFrEF) for the treatment of congestion; however, they might hamper uptitration of inhibitors of the renin\u2013angiotensin system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Loop diuretic dose at baseline was recorded in 2338 patients with HFrEF enrolled in BIOSTAT-CHF, an international study of HF patients on loop diuretic therapy who were eligible for uptitration of angiotensin-converting enzyme inhibitors (ACEi)\/mineralocorticoid receptor antagonists (MRA). The association between loop diuretic dose and uptitration of ACEi\/MRA to percentage of target dose was adjusted for a previously published model for likelihood of uptitration and a propensity score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Baseline median loop diuretic dose was 40 [40\u2013100] mg of furosemide or equivalent. Higher doses of loop diuretics were associated with higher NYHA class and higher levels of NT-proBNP, more severe signs and symptoms of congestion, more frequent MRA use, and lower doses of ACEi reached at 3 and 9\u00a0months (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.01). After propensity adjustment, higher doses of loop diuretics remained significantly associated with poorer uptitration of ACEi (Beta per log doubling of loop diuretic dose: \u2212\u00a01.66,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.021), but not with uptitration of MRAs (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.758). Higher doses of loop diuretics were independently associated with an increased risk of all-cause mortality or HF hospitalization [HR per doubling of loop diuretic dose: 1.06 (1.01\u20131.12),\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.021].\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Higher doses of loop diuretics limited uptitration of ACEi in patients with HFrEF and were associated with a higher risk of death and\/or HF hospitalization, independent of their lower likelihood of uptitration and higher baseline risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphic abstract<\/jats:title>\n                    <jats:p>This figure was created with images adapted from Servier Medical Art licensed under a Creative Commons Attribution 3.0<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00392-020-01598-w","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T13:02:36Z","timestamp":1580389356000},"page":"1048-1059","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Higher doses of loop diuretics limit uptitration of angiotensin-converting enzyme inhibitors in patients with heart failure and reduced ejection fraction"],"prefix":"10.1007","volume":"109","author":[{"given":"Jozine M.","family":"ter Maaten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Martens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Damman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chim C.","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leong L.","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilesh J.","family":"Samani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Cleland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans L.","family":"Hillege","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Metra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8547-2992","authenticated-orcid":false,"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Mullens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,30]]},"reference":[{"key":"1598_CR1","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1054\/jcaf.2003.25","volume":"9","author":"P Faggiano","year":"2003","unstructured":"Faggiano P, Opasich C, Tavazzi L et al (2003) Prescription patterns of diuretics in chronic heart failure: a contemporary background as a clue to their role in treatment. 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Saunders Elsevier, Philadelphia"}],"container-title":["Clinical Research in Cardiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00392-020-01598-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00392-020-01598-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00392-020-01598-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T19:27:19Z","timestamp":1611862039000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00392-020-01598-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,30]]},"references-count":22,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["1598"],"URL":"https:\/\/doi.org\/10.1007\/s00392-020-01598-w","relation":{},"ISSN":["1861-0684","1861-0692"],"issn-type":[{"value":"1861-0684","type":"print"},{"value":"1861-0692","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,30]]},"assertion":[{"value":"9 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The University Medical Centre Groningen, which employs several authors, has received research grants and\/or fees from AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Roche, Trevena, and ThermoFisher GmbH. AAV received consultancy fees and\/or research grants from: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, GSK, Novartis, Roche Diagnostics, Servier. CCL received consultancy fees and\/or research grants from Amgen, Astra Zeneca, MSD, Novartis, and Servier. DJvV reports board membership fess\/travel expenses from BioControl, Cardiorentis, Johnson & Johnson, Novartis, Vifor, and Zoll Medical. KDickstein has received honorario and\/or research support from Medtronic, Boston Scientific St Jude, Biotronik and Sorin, and Merck, Novartis, Amgen, Boehringer Ingelheim, Astra Zeneca, Pfizer, Bayer, GSK, Rohce, Sanofi, Abbott, Otsuka, Leo, Servier, and Bristol Meyers Squibb. GF reports committee membership in trials and \/or registries sponsored by Bayer, Novartis, BI, Medtronic, Vifor, Servier. MM has received consulting honorario from Amgen, Astro Zeneca, Novartis, Relypsa, and Serviers, and speaker\u2019s fees from Abbott Vascular and Servier. PM has received consultancy fees from Novartis, Vifor Pharma, Boehringer Ingelheim, and AstraZeneca, and an unrestricted research grant from Vifor Pharma. SDA reports grants from Vifor and Abbott Vascular,\u00a0and fees for consultancy from Vifor, Bayer, Boehringer Ingelheim, Brahms,\u00a0Janssen, Novartis, Servier, and\u00a0Stealth Pepitdes. WM has received research grants from Novartis, Vifor, Medtronic, Biotronik, Abbott, and Boston Scientific.\u00a0JMtM, JGC, FZ, HLH, LLN, NJS, KDamman, and PP have nothing to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}