{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:30:31Z","timestamp":1774431031749,"version":"3.50.1"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Evidence regarding the prognostic impact of angiotensin-converting enzyme inhibitors (ACEi) vs. receptor blockers (ARB) in heart failure with mildly reduced ejection fraction (HFmrEF) is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively studied consecutive patients hospitalized with HFmrEF from 2016 until 2022 at a German university hospital. The prognostic impact of treatment with ACEi compared with ARB was investigated regarding the primary endpoint of all-cause mortality at 30 months. The key secondary endpoint was heart failure (HF)\u2013related rehospitalization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 1,551 patients discharged on renin\u2013angiotensin system inhibitors (ACEi:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091,055; ARB:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009496) were included. Patients treated with ARB were older and had a higher burden of comorbidities. All-cause mortality at 30 months occurred in 251\/1,055 (23.8%) patients treated with ACEi and in 147\/496 (29.6%) patients treated with ARB [unadjusted hazard ratio [HR]\u2009=\u20090.762, 95% confidence interval [CI] 0.622\u20130.934; log-rank\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009]. After multivariable adjustment, ACEi were still associated with improved long-term survival (adjusted HR\u2009=\u20090.786, 95% CI: 0.625\u20130.989;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.040). This association was still found after propensity score matching (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009440 per group) (23.2% vs. 29.5%; HR\u2009=\u20090.749, 95% CI: 0.578\u20130.971;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.029). In contrast, the risk of HF-related rehospitalization at 30 months did not differ between the two groups in the unmatched cohort (12.7% vs. 14.5%; HR\u2009=\u20090.849, 95% CI: 0.638\u20131.130;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.262) and after propensity score matching (16.1% vs. 14.8%; HR\u2009=\u20091.080, 95% CI: 0.772\u20131.512;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.653).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients hospitalized with HFmrEF, ACEi therapy was associated with reduced 30-month all-cause mortality compared with ARB, whereas the risk of HF-related rehospitalization did not differ.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1753965","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:56:26Z","timestamp":1774421786000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Angiotensin-converting enzyme inhibitors vs. receptor blockers in heart failure with mildly reduced ejection fraction"],"prefix":"10.3389","volume":"13","author":[{"given":"Kathrin","family":"Weidner","sequence":"first","affiliation":[{"name":"Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Behnes","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marielen","family":"Reinhardt","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noah","family":"Abel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henning Johann","family":"Steffen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Hetjens","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, University of Heidelberg","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Duerschmied","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim","family":"Akin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Schupp","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University","place":["Mannheim, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1002\/ejhf.1858","article-title":"Epidemiology of heart failure","volume":"22","author":"Groenewegen","year":"2020","journal-title":"Eur J Heart Fail"},{"key":"B2","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":"B3","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1002\/ejhf.945","article-title":"A comprehensive population-based characterization of heart failure with mid-range ejection fraction","volume":"19","author":"Koh","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"B4","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ejim.2022.05.030","article-title":"From mid-range to mildly reduced ejection fraction heart failure: a call to treat","volume":"103","author":"Stolfo","year":"2022","journal-title":"Eur J Intern Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1822","DOI":"10.1002\/ehf2.14284","article-title":"The impact of heart failure therapy in patients with mildly reduced ejection fraction: a network meta-analysis","volume":"10","author":"Leite","year":"2023","journal-title":"ESC Heart Fail"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2512","DOI":"10.1038\/s41591-022-02041-5","article-title":"Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-preserved","volume":"28","author":"Anker","year":"2022","journal-title":"Nat Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e0239100","DOI":"10.1371\/journal.pone.0239100","article-title":"Impact of left ventricular ejection fraction on the effect of renin-angiotensin system blockers after an episode of acute heart failure: from the KCHF registry","volume":"15","author":"Yoshikawa","year":"2020","journal-title":"PLoS One"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1016\/S0140-6736(00)02213-3","article-title":"Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial\u2013the losartan heart failure survival study ELITE II","volume":"355","author":"Pitt","year":"2000","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/S0140-6736(02)09895-1","article-title":"Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal trial in myocardial infarction with angiotensin II antagonist losartan","volume":"360","author":"Dickstein","year":"2002","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1056\/NEJMoa032292","article-title":"Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both","volume":"349","author":"Pfeffer","year":"2003","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1056\/NEJMoa0805450","article-title":"Irbesartan in patients with heart failure and preserved ejection fraction","volume":"359","author":"Massie","year":"2008","journal-title":"N Engl J Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"70","DOI":"10.15420\/cfr.2018.11.2","article-title":"Heart failure with mid-range ejection fraction: lessons from CHARM","volume":"4","author":"Lund","year":"2018","journal-title":"Card Fail Rev"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1093\/ehjci\/jeaa266","article-title":"Training, competence, and quality improvement in echocardiography: the European association of cardiovascular imaging recommendations: update 2020","volume":"21","author":"Popescu","year":"2020","journal-title":"Eur Heart J Cardiovasc Imaging"},{"key":"B14","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1001\/jama.2010.1949","article-title":"Association of candesartan vs losartan with all-cause mortality in patients with heart failure","volume":"305","author":"Eklind-Cervenka","year":"2011","journal-title":"JAMA"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1093\/eurjpc\/zwae121","article-title":"Effect of heart failure pharmacotherapies in patients with heart failure with mildly reduced ejection fraction","volume":"31","author":"Schupp","year":"2024","journal-title":"Eur J Prev Cardiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/s10557-018-6812-z","article-title":"Beta-blockers and ACE inhibitors are associated with improved survival secondary to ventricular tachyarrhythmia","volume":"32","author":"Schupp","year":"2018","journal-title":"Cardiovasc Drugs Ther"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.3390\/jcm11051460","article-title":"Angiotensin converting enzyme inhibitors versus receptor blockers in patients with ventricular tachyarrhythmias","volume":"11","author":"Schupp","year":"2022","journal-title":"J Clin Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/S0140-6736(03)14285-7","article-title":"Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-preserved trial","volume":"362","author":"Yusuf","year":"2003","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1001\/jama.2012.452","article-title":"Association of treatment with losartan vs candesartan and mortality among patients with heart failure","volume":"307","author":"Svanstrom","year":"2012","journal-title":"JAMA"},{"key":"B20","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/S1357-2725(02)00273-X","article-title":"Bradykinin, angiotensin-(1-7), and ACE inhibitors: how do they interact?","volume":"35","author":"Tom","year":"2003","journal-title":"Int J Biochem Cell Biol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1056\/NEJMoa1409077","article-title":"Angiotensin-neprilysin inhibition versus enalapril in heart failure","volume":"371","author":"McMurray","year":"2014","journal-title":"N Engl J Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1056\/NEJMoa1908655","article-title":"Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction","volume":"382","author":"Solomon","year":"2020","journal-title":"N Engl J Med"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1753965\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:56:28Z","timestamp":1774421788000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1753965\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":22,"alternative-id":["10.3389\/fcvm.2026.1753965"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1753965","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"article-number":"1753965"}}