{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:57:57Z","timestamp":1793829477291,"version":"4.6.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"25","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014470","name":"Netherlands Heart Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014470","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020604","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020604","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019718","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014091","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014091","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019189","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001316","name":"Abbott","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001316","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006484","name":"Vifor Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Despite guidelines recommending rapid initiation and up-titration of Guideline-recommended medical therapy (GRMT) for heart failure (HF) with reduced ejection fraction (HFrEF), its feasibility in daily practice remains unclear. TITRATE-HF studies the feasibility of rapid GRMT implementation in de novo HFrEF patients, investigating titration patterns and identifying barriers to effective treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This analysis focuses on the de novo HFrEF patients included in the TITRATE-HF study, an ongoing prospective HF registry conducted in 48 Dutch hospitals. A detailed logbook for each GRMT drug class was recorded, from diagnosis to six months, including initiations, dose adjustments, discontinuations, and reasons for changes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The study included 1508 de novo HFrEF patients (median age: 70 years [inter-quartile ranges, IQR 62\u201377]; 31% women; median left ventricular ejection fraction: 30% [IQR 25\u201335]). At 6 weeks, 46% of patients were using quadruple therapy. Within 6 weeks post-HFrEF diagnosis, 50% of patients were prescribed quadruple therapy at some point, with 84% remaining on it after 180 days. At 6 months, 66.3% of patients were prescribed quadruple therapy, but only 1.3% achieved target doses for all four drug classes. While side effects accounted for 20%\u201337% of cases where target doses were not reached, a large proportion was attributed to physicians accepting suboptimal doses. Drug titrations occurred frequently in the first 60 days after diagnosis, fading afterwards. Discontinuation rates for angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, angiotensin receptor\u2013neprilysin inhibitors, beta-blocker, mineralocorticoid receptor antagonists, and sodium\u2013glucose cotransporter 2 inhibitors were 13%, 11%, 9%, 9%, 11%, and 9%, respectively, primarily due to side effects or intolerances. Rechallenging these drug classes was successful in over 83% of patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The TITRATE-HF study demonstrates that rapid initiation of GRMT for HFrEF is feasible in real-world clinical practice. Nonetheless, our results highlight the urgency for a proactive approach and ongoing dose titration of pharmacological therapy beyond the initial first months to fully optimize treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehaf244","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T19:55:06Z","timestamp":1743278106000},"page":"2394-2405","source":"Crossref","is-referenced-by-count":34,"title":["Newly diagnosed heart failure with reduced ejection fraction: timing, sequencing, and titration of guideline-recommended medical therapy"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1561-3542","authenticated-orcid":false,"given":"Jishnu","family":"Malgie","sequence":"first","affiliation":[{"name":"Cardiovascular Institute, Thorax Center, Department of Cardiology, Erasmus MC , Dr. Molewaterplein 40, 3015 GD Rotterdam ,","place":["The 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E","family":"Emans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Ikazia Ziekenhuis , Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grytsje A","family":"De Boer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Meander Medical Centre , Amersfoort ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte E P","family":"Siegers","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Noordwest Hospital Group , Alkmaar ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius M W","family":"van Stipdonk","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Centre , Maastricht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander 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