{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:40:13Z","timestamp":1791247213406,"version":"4.1.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020676","name":"IRCCS Policlinico San Donato","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020676","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bando Ricerca Indipendente Code AIFA-Cardio-129"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Despite the advancements in the treatment of patients with heart failure with reduced ejection fraction (HFrEF), clinical inertia regarding the prescription of the four classes of guideline-directed medical therapies (GDMT) remains prevalent. This study aims to assess how adherence and time of prescription to GDMT in HFrEF impact mortality. Additionally, it seeks to evaluate sex differences in prescription and outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The study retrospectively analysed data worldwide using the TriNetX database. Patients with HFrEF were divided into four groups (G1\u2013G4) based on the number of classes of GDMT prescribed. The primary endpoint was all-cause mortality. Additional analysis was performed in the G4 group to examine the impact of the time to reach quadruple therapy on mortality. An age-matched subgroup analysis was conducted to assess whether sex influenced mortality. The total cohort included 17 668 patients (68% men, mean age 66.7 \u00b1 14.6). Only 20% of patients received quadruple therapy; the least heart failure (HF) medications prescribed were mineralocorticoid receptor antagonists (39%) and sodium-glucose cotransporter-2 inhibitors (33%), especially among older and frail patients. Each additional HF therapy was associated with significant mortality reduction (P-value &amp;lt; 0.001 for each additional class prescribed). However, the timing of full treatment implementation within the first year did not significantly affect mortality in the G4 group. No significant sex-based differences in survival were found in the age-matched analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Clinical inertia remains a critical issue, especially in those who may most benefit from HF therapy. Further clinical trials should specifically assess sex-related differences in drug efficacy and patient characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay summary<\/jats:title>\n                    <jats:p>Heart failure with reduced ejection fraction is a serious condition that affects many people worldwide. This study looked at how well heart failure medications are being used and their impact on survival. Out of all patients included, only a small percentage received all the recommended treatments, even though using more medications was linked to better survival. Differences between men and women were also noted, with women being older and having more health problems, but survival rates were similar when comparing men and women of the same age. These results highlight the need for better treatment approaches to improve outcomes for all patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjqcco\/qcaf095","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T11:38:30Z","timestamp":1755949110000},"page":"1369-1376","source":"Crossref","is-referenced-by-count":20,"title":["Global real-world data on heart failure with reduced ejection fraction: challenges in optimization and sex disparities"],"prefix":"10.1093","volume":"11","author":[{"given":"Andrea","family":"Attanasio","sequence":"first","affiliation":[{"name":"Cardiology University Department, IRCCS Policlinico San Donato, Via Morandi 30 , San Donato Milanese 20097 ,","place":["Italy"]},{"name":"Multimodality Cardiac Imaging Unit, IRCCS Policlinico San Donato , Via Morandi 30, San Donato Milanese 20097 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5666-8368","authenticated-orcid":false,"given":"Gianluigi","family":"Guida","sequence":"additional","affiliation":[{"name":"Cardiology University Department, IRCCS Policlinico San Donato, Via Morandi 30 , San Donato Milanese 20097 ,","place":["Italy"]},{"name":"Multimodality Cardiac Imaging Unit, IRCCS Policlinico San Donato , Via Morandi 30, San Donato Milanese 20097 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1024-1644","authenticated-orcid":false,"given":"Giandomenico","family":"Disabato","sequence":"additional","affiliation":[{"name":"Cardiology University Department, IRCCS Policlinico San Donato, Via Morandi 30 , San Donato Milanese 20097 ,","place":["Italy"]},{"name":"Multimodality Cardiac Imaging Unit, IRCCS Policlinico San Donato , Via Morandi 30, San Donato Milanese 20097 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Girani","sequence":"additional","affiliation":[{"name":"Laboratory of Biostatistics and Data Management, Scientific Directorate, IRCCS Policlinico San Donato , Via Morandi 30, San Donato Milanese 20097 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3144-9364","authenticated-orcid":false,"given":"Sara","family":"Boveri","sequence":"additional","affiliation":[{"name":"Laboratory of Biostatistics and Data Management, Scientific Directorate, IRCCS Policlinico San Donato , Via Morandi 30, San Donato Milanese 20097 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Paglione","sequence":"additional","affiliation":[{"name":"Health Professions Research and Development Unit, IRCCS Policlinico San Donato , Via Morandi 30, San Donato Milanese 20097 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Giardino","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Federico II University , Via Sergio Pansini 5, Naples 80131 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin","family":"Iannotta","sequence":"additional","affiliation":[{"name":"University of Milan , Via festa del perdono 7, Milan 20122 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-7063","authenticated-orcid":false,"given":"Serenella","family":"Castelvecchio","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Prevention and Gender Medicine, I.R.C.C.S Policlinico San Donato , San Donato Milanese 20097 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Piepoli","sequence":"additional","affiliation":[{"name":"Cardiology University Department, IRCCS Policlinico San Donato, Via Morandi 30 , San Donato Milanese 20097 ,","place":["Italy"]},{"name":"Department of Biomedical Sciences for Health, University of Milan , Via Carlo Pascal 36, Milan 20133 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"2025121818532437800_qcaf095-B1","doi-asserted-by":"crossref","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":"2025121818532437800_qcaf095-B2","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1002\/ejhf.3295","article-title":"How to tackle therapeutic inertia in heart failure with reduced ejection fraction. 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