{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:02:39Z","timestamp":1792818159849,"version":"4.5.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":283,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Novartis Healthcare A\/S, Denmark"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We aimed to assess real-world implementation of guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF) and its association with mortality and hospitalization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed 46 816 incident HFrEF patients from the Danish Heart Failure Registry (2008\u20132022). We examined the utilization of GDMT\u2014renin\u2013angiotensin system inhibitors (RASi), beta-blockers, mineralocorticoid receptor antagonists (MRAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i)\u2014at 4, 8 and 12 weeks of follow-up according to the European Society of Cardiology guidelines within the intervals 2008\u20132011, 2012\u20132015, 2016\u20132020 and 2021\u20132022. Using Cox regression, we assessed the associations between GDMTs [none (reference), 1\u20132 GDMTs, and 3\u20134 GDMTs] initiated at 4, 8 and 12 weeks and 1 and 3 year mortality (all-cause and cardiovascular) and hospitalization (all-cause and HF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between 2008\u20132011 and 2021\u20132022, RASi utilization at 4 weeks of follow-up was 93.2% and 93.7%, respectively, and at 12 weeks of follow-up, 97.2% and 97.8%, respectively. Beta-blocker use was 81.1% and 78.2% at 4 weeks and 89.6% and 90.4% at 12 weeks of follow-up while MRA utilization was 27.2% and 34.6% at 4 weeks and 32.6% and 52.2% at 12 weeks of follow-up. The SGLT2i use at 4 weeks increased from 0.0% to 21.3%, and at 12 weeks of follow-up from 3.2% to 35.8% between 2016\u20132020 and 2021\u20132022. The initiation of GDMTs at 4 weeks of follow-up was associated with lower adjusted hazard ratios (HRs) [95% confidence intervals (CI)] for 1 year all-cause mortality [1\u20132 GDMTs: 0.73 (95% CI: 0.61\u20130.86), 3\u20134 GDMTs: 0.65 (95% CI: 0.55\u20130.78)], 3 year all-cause mortality [1\u20132 GDMTs: 0.75 (95% CI: 0.66\u20130.86); 3\u20134 GDMTs: 0.67 (95% CI: 0.59\u20130.76)] and 3 year cardiovascular mortality [1\u20132 GDMTs: 0.74 (95% CI: 0.62\u20130.89); 3\u20134 GDMTs: 0.72 (95% CI: 0.59\u20130.87)]. Lower adjusted HRs were also observed for 1 year all-cause hospitalization [1\u20132 GDMTs: 0.80 (95% CI: 0.75\u20130.86); 3\u20134 GDMTs: 0.78 (95% CI: 0.73\u20130.84)] and 3 year all-cause hospitalization [1\u20132 GDMTs: 0.77 (95% CI: 0.72\u20130.83); 3\u20134 GDMTs: 0.77 (95% CI: 0.71\u20130.82)].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrated high use of RASi and beta-blockers and rising use of MRA and SGLT2i, reflecting rapid adaption to guidelines changes in incident HFrEF patients. Early GDMT initiation was associated with lower 1 and 3 year mortality and all-cause hospitalization. Upfront treatment with GDMT, according to the latest guidelines, is crucial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.15320","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:09:18Z","timestamp":1747008558000},"page":"3003-3017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Real-World Use of Guideline-Directed Therapy for Heart Failure: Insights From the Danish Heart Failure Registry"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4086-2281","authenticated-orcid":false,"given":"Inge","family":"Schj\u00f8dt","sequence":"first","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan B.","family":"Valentin","sequence":"additional","affiliation":[{"name":"Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University , Aalborg ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren P.","family":"Johnsen","sequence":"additional","affiliation":[{"name":"Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University , Aalborg ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke E.","family":"Mols","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital , Aarhus ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Aarhus University , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Egstrup","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Unit, Odense University Hospital , Svendborg ,","place":["Denmark"]},{"name":"Cardiovascular Center of Excellence, Odense University Hospital , Odense ,","place":["Denmark"]},{"name":"Steno Diabetes Center Odense, Odense University Hospital , Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian B.","family":"L\u00f8gstrup","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital , Aarhus ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Aarhus University , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,11]]},"reference":[{"key":"2026021804161271900_ehf215320-bib-0001","doi-asserted-by":"publisher","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":"2026021804161271900_ehf215320-bib-0002","doi-asserted-by":"publisher","first-page":"3272","DOI":"10.1093\/cvr\/cvac013","article-title":"Global burden of heart failure: a comprehensive and updated review of epidemiology","volume":"118","author":"Savarese","year":"2023","journal-title":"Cardiovasc Res"},{"key":"2026021804161271900_ehf215320-bib-0003","doi-asserted-by":"publisher","first-page":"e895","DOI":"10.1161\/CIR.0000000000001063","article-title":"2022 AHA\/ACC\/HFSA guideline for the Management of Heart Failure: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"2026021804161271900_ehf215320-bib-0004","doi-asserted-by":"publisher","first-page":"294","DOI":"10.4070\/kcj.2023.0024","article-title":"Treatment strategies of improving quality of care in patients with heart failure","volume":"53","author":"Kim","year":"2023","journal-title":"Korean Circ J"},{"key":"2026021804161271900_ehf215320-bib-0005","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jchf.2022.08.009","article-title":"Heart failure drug treatment-inertia, titration, and discontinuation: a multinational observational study (EVOLUTION HF)","volume":"11","author":"Savarese","year":"2023","journal-title":"JACC Heart Fail"},{"key":"2026021804161271900_ehf215320-bib-0006","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1002\/ejhf.2483","article-title":"Use of evidence-based therapy in heart failure with reduced ejection fraction across age strata","volume":"24","author":"Stolfo","year":"2022","journal-title":"Eur J Heart Fail"},{"key":"2026021804161271900_ehf215320-bib-0007","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1016\/j.ejheart.2008.08.005","article-title":"ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. 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