{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:35:35Z","timestamp":1791318935633,"version":"4.3.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To assess the association between combination, dose and use of current guideline\u2010recommended target doses (TD) of renin\u2013angiotensin system inhibitors (RASi), angiotensin receptor\u2013neprilysin inhibitors (ARNi) and \u03b2\u2010blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure (HF) and reduced ejection fraction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Overall, 17\u2009809 outpatients registered in the Swedish Heart Failure Registry (SwedeHF) from May 2000 to December 2018, with ejection fraction &lt;40% and duration of HF \u226590\u2009days were selected. Primary outcome was a composite of time to cardiovascular death and first HF hospitalization. Compared with no use of RASi or ARNi, the adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.83 (0.76\u20130.91) with &lt;50% of TD, 0.78 (0.71\u20130.86) with 50%\u201399%, and 0.73 (0.67\u20130.80) with \u2265100% of TD. Compared with no use of \u03b2\u2010blockers, the adjusted HR (95% CI) was 0.86 (0.76\u20130.91), 0.81 (0.74\u20130.89) and 0.74 (0.68\u20130.82) with &lt;50%, 50%\u201399% and \u2265100% of TD, respectively. Patients receiving both an angiotensin\u2010converting enzyme inhibitor (ACEi)\/angiotensin receptor blocker (ARB)\/ARNi and a \u03b2\u2010blocker at 50%\u201399% of TD had a lower adjusted risk of the primary outcome compared with patients only receiving one drug, i.e. ACEi\/ARB\/ARNi or \u03b2\u2010blocker, even if this was at \u2265100% of TD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Heart failure with reduced ejection fraction patients using higher doses of RASi or ARNi and \u03b2\u2010blockers had lower risk of cardiovascular death or HF hospitalization. Use of two drug classes at 50%\u201399% of TD dose was associated with lower risk than one drug class at 100% of TD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2477","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T04:15:07Z","timestamp":1646712907000},"page":"871-884","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Association between dosing and combination use of medications and outcomes in heart failure with reduced ejection fraction: data from the\n                    <scp>S<\/scp>\n                    wedish Heart Failure Registry"],"prefix":"10.1093","volume":"24","author":[{"given":"Domenico","family":"D'Amario","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Cardiovascular Sciences Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"},{"name":"Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4690-725X","authenticated-orcid":false,"given":"Daniele","family":"Rodolico","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6868-4248","authenticated-orcid":false,"given":"Giuseppe M.C.","family":"Rosano","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences IRCCS San Raffaele  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6353-8041","authenticated-orcid":false,"given":"Ulf","family":"Dahlstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Cardiology and the Department of Health, Medicine and Caring Sciences Linkoping University  Linkoping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9482-411X","authenticated-orcid":false,"given":"Filippo","family":"Crea","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"},{"name":"Department of Cardiovascular and Pulmonary Sciences Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1411-4482","authenticated-orcid":false,"given":"Lars H.","family":"Lund","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine Karolinska Institutet  Stockholm Sweden"},{"name":"Heart and Vascular Theme Karolinska University Hospital  Stockholm Sweden"}],"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  Stockholm Sweden"},{"name":"Heart and Vascular Theme Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l223"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199605233342101"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)04440-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)74354-3"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198706043162301"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250501"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199209033271001"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409077"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw128"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hft134"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2018.10.010"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.13237"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.04.070"},{"key":"e_1_2_6_15_1","first-page":"e1008","article-title":"Prescribing patterns of evidence\u2010based heart failure pharmacotherapy and outcomes in the ASIAN\u2010HF registry: a cohort study. 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