{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T08:00:58Z","timestamp":1794211258613,"version":"4.8.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Guideline recommendations for the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) derive from small subgroups in post-hoc analyses of randomized trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We investigated predictors of renin\u2013angiotensin system inhibitors\/angiotensin receptor neprilysin inhibitors (RASI\/ARNI) and beta-blockers use, and the associations between these medications and mortality\/morbidity in a large real-world cohort with HFmrEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Patients with HFmrEF (EF 40\u201349%) from the Swedish HF Registry were included. The associations between medications and cardiovascular (CV) mortality\/HF hospitalization (HFH), and all-cause mortality were assessed through Cox regressions in a 1:1 propensity score-matched cohort. A positive control analysis was performed in patients with EF\u00a0&amp;lt;\u00a040%, while a negative control outcome analysis had cancer-related hospitalization as endpoint. Of 12\u00a0421 patients with HFmrEF, 84% received RASI\/ARNI and 88% beta-blockers. Shared-independent predictors of RASI\/ARNI and beta-blockers use were younger age, being an outpatient, follow-up in specialty care, and hypertension. In the matched cohorts, use of both RASI\/ARNI and beta-blocker use was separately associated with lower risk of CV mortality\/HFH [hazard ratio (HR)\u00a0=\u00a00.90, 95% confidence interval (CI): 0.83\u20130.98 and HR\u00a0=\u00a00.82, 95% CI: 0.74\u20130.90, respectively] and of all-cause mortality (HR\u00a0=\u00a00.75, 95% CI: 0.69\u20130.81 and HR\u00a0=\u00a00.79, 95% CI: 0.72\u20130.87, respectively). Results were consistent at the positive control analysis, and there were no associations between treatment use and the negative control outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RASI\/ARNI and beta-blockers were extensively used in this large real-world cohort with HFmrEF. Their use was safe since associated with lower mortality and morbidity. Our findings confirm the real-world evidence from previous post-hoc analyses of trials, and represent a further call for implementing guideline recommendations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjcvp\/pvad036","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T06:47:45Z","timestamp":1684478865000},"page":"526-535","source":"Crossref","is-referenced-by-count":20,"title":["Heart failure pharmacological treatments and outcomes in heart failure with mildly reduced ejection fraction"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4538-6811","authenticated-orcid":false,"given":"Davide","family":"Stolfo","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Karolinska Institutet, Heart, Vascular and Neuro Theme Karolinska University Hospital, Norrbacka S3:00, Stockholm 171 76 , Sweden"},{"name":"Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Univeristy Hospital of Trieste , Trieste , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars H","family":"Lund","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Karolinska Institutet, Heart, Vascular and Neuro Theme Karolinska University Hospital, Norrbacka S3:00, Stockholm 171 76 , Sweden"},{"name":"Heart, Vascular and Neuro Theme, Karolinska University Hospital , Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2700-8478","authenticated-orcid":false,"given":"Gianfranco","family":"Sinagra","sequence":"additional","affiliation":[{"name":"Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Univeristy Hospital of Trieste , Trieste , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Lindberg","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Karolinska Institutet, Heart, Vascular and Neuro Theme Karolinska University Hospital, Norrbacka S3:00, Stockholm 171 76 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Dahlstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Department of Health, Medicine and Caring Sciences, Linkoping University , Linkoping , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6868-4248","authenticated-orcid":false,"given":"Giuseppe","family":"Rosano","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, IRCCS San Raffaele , Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7732-0887","authenticated-orcid":false,"given":"Gianluigi","family":"Savarese","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Karolinska Institutet, Heart, Vascular and Neuro Theme Karolinska University Hospital, Norrbacka S3:00, Stockholm 171 76 , Sweden"},{"name":"Heart, Vascular and Neuro Theme, Karolinska University Hospital , Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"2023092007135295000_bib1","doi-asserted-by":"crossref","first-page":"l223","DOI":"10.1136\/bmj.l223","article-title":"Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017: population based cohort study","volume":"364","author":"Taylor","year":"2019","journal-title":"BMJ"},{"key":"2023092007135295000_bib2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/ejhf.496","article-title":"Use of evidence-based therapy and survival in heart failure in Sweden 2003\u20132012","volume":"18","author":"Thorvaldsen","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2023092007135295000_bib3","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/j.jacc.2013.11.053","article-title":"The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries","volume":"63","author":"Ambrosy","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"2023092007135295000_bib4","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur Heart J"},{"key":"2023092007135295000_bib5","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":"2023092007135295000_bib6","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41569-021-00605-5","article-title":"Heart failure with mid-range or mildly reduced ejection fraction","volume":"19","author":"Savarese","year":"2022","journal-title":"Nat Rev Cardiol"},{"key":"2023092007135295000_bib7","first-page":"e895","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":"2023092007135295000_bib8","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/ejhf.2115","article-title":"Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association","volume":"23","author":"Bozkurt","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"2023092007135295000_bib9","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1002\/ejhf.1160","article-title":"Effect of digoxin in patients with heart failure and mid-range (borderline) left ventricular ejection fraction","volume":"20","author":"Abdul-Rahim","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"2023092007135295000_bib10","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1093\/eurheartj\/ehx564","article-title":"Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials","volume":"39","author":"Cleland","year":"2018","journal-title":"Eur Heart J"},{"key":"2023092007135295000_bib11","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1002\/ejhf.1149","article-title":"Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum","volume":"20","author":"Lund","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"2023092007135295000_bib12","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1161\/CIRCULATIONAHA.119.044586","article-title":"Sacubitril\/valsartan across the spectrum of ejection fraction in heart failure","volume":"141","author":"Solomon","year":"2020","journal-title":"Circulation"},{"key":"2023092007135295000_bib13","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/eurheartj\/ehv464","article-title":"Influence of ejection fraction on outcomes and efficacy of spironolactone in patients with heart failure with preserved ejection fraction","volume":"37","author":"Solomon","year":"2016","journal-title":"Eur Heart J"},{"key":"2023092007135295000_bib14","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJMoa2107038","article-title":"Empagliflozin in heart failure with a preserved ejection fraction","volume":"385","author":"Anker","year":"2021","journal-title":"N Engl J Med"},{"key":"2023092007135295000_bib15","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1056\/NEJMoa2206286","article-title":"Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction","volume":"387","author":"Solomon","year":"2022","journal-title":"N Engl J Med"},{"key":"2023092007135295000_bib16","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1177\/0962280212445945","article-title":"A comparison of two methods of estimating propensity scores after multiple imputation","volume":"25","author":"Mitra","year":"2016","journal-title":"Stat Methods Med Res"},{"key":"2023092007135295000_bib17","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1002\/ejhf.813","article-title":"Epidemiology and one-year outcomes in patients with chronic heart failure and preserved, mid-range and reduced ejection fraction: an analysis of the ESC Heart Failure Long-Term Registry","volume":"19","author":"Chioncel","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"2023092007135295000_bib18","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1002\/ejhf.807","article-title":"Characterization of heart failure patients with mid-range left ventricular ejection fraction-a report from the CHART-2 Study","volume":"19","author":"Tsuji","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"2023092007135295000_bib19","doi-asserted-by":"crossref","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":"2023092007135295000_bib20","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41569-021-00605-5","article-title":"Heart failure with mid-range or mildly reduced ejection fraction","volume":"19","author":"Savarese","year":"2022","journal-title":"Nat Rev Cardiol"},{"key":"2023092007135295000_bib21","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ijcard.2020.04.068","article-title":"Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: a blueprint for clinical trial design","volume":"313","author":"Savarese","year":"2020","journal-title":"Int J Cardiol"},{"key":"2023092007135295000_bib22","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0140-6736(18)32484-X","article-title":"Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial","volume":"393","author":"Halliday","year":"2019","journal-title":"Lancet North Am Ed"},{"key":"2023092007135295000_bib23","doi-asserted-by":"crossref","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":"2023092007135295000_bib24","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/ehf2.13848","article-title":"Patient profile and outcomes associated with follow-up in specialty vs. primary care in heart failure","volume":"9","author":"Lindberg","year":"2022","journal-title":"ESC Heart Fail"},{"key":"2023092007135295000_bib25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/ejhf.1329","article-title":"Introducing nurse-led heart failure clinics in Swedish primary care settings","volume":"21","author":"Liljeroos","year":"2019","journal-title":"Eur J Heart Fail"},{"key":"2023092007135295000_bib26","first-page":"505","article-title":"Sex-based differences in heart failure across the ejection fraction spectrum: phenotyping, and prognostic and therapeutic implications","volume":"7","author":"Stolfo","year":"2019","journal-title":"JACC: Heart Fail"},{"key":"2023092007135295000_bib27","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jacc.2018.04.070","article-title":"Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF Registry","volume":"72","author":"Greene","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2023092007135295000_bib28","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1056\/NEJMoa1908142","article-title":"Metoprolol for the prevention of acute exacerbations of COPD","volume":"381","author":"Dransfield","year":"2019","journal-title":"N Engl J Med"},{"key":"2023092007135295000_bib29","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1056\/NEJMoa1908655","article-title":"Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction","volume":"381","author":"Solomon","year":"2019","journal-title":"N Engl J Med"},{"key":"2023092007135295000_bib30","first-page":"306","article-title":"Prevalence and prognostic implications of longitudinal ejection fraction change in heart failure","volume":"7","author":"Savarese","year":"2019","journal-title":"JACC: Heart Fail"},{"key":"2023092007135295000_bib31","first-page":"174","article-title":"Association of spironolactone use with all-cause mortality in heart failure: a propensity scored cohort study","volume":"6","author":"Lund","year":"2013","journal-title":"Circ: Heart Fail"},{"key":"2023092007135295000_bib32","volume-title":"Final Summary Minutes of the Cardiovascular and Renal Drugs Advisory Committee Meeting 16 December 2020","author":"Administration USFaD","year":"2020"}],"container-title":["European Heart Journal - Cardiovascular Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ehjcvp\/advance-article-pdf\/doi\/10.1093\/ehjcvp\/pvad036\/50625964\/pvad036.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article-pdf\/9\/6\/526\/51686195\/pvad036.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article-pdf\/9\/6\/526\/51686195\/pvad036.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T03:14:50Z","timestamp":1695179690000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article\/9\/6\/526\/7172855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,18]]},"references-count":32,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,5,18]]},"published-print":{"date-parts":[[2023,9,20]]}},"URL":"https:\/\/doi.org\/10.1093\/ehjcvp\/pvad036","relation":{},"ISSN":["2055-6837","2055-6845"],"issn-type":[{"value":"2055-6837","type":"print"},{"value":"2055-6845","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,9]]},"published":{"date-parts":[[2023,5,18]]}}}