{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T03:34:59Z","timestamp":1781235299671,"version":"3.54.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T00:00:00Z","timestamp":1585094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010525","name":"NHS Education for Scotland","doi-asserted-by":"publisher","award":["PCL\/17\/07"],"award-info":[{"award-number":["PCL\/17\/07"]}],"id":[{"id":"10.13039\/100010525","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Several studies have shown that older patients with heart failure with reduced ejection fraction (HFrEF) are undertreated. The aim of this study was to evaluate the association of up\u2010titration of angiotensin\u2010converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) and beta\u2010blockers on outcome across the age spectrum in HFrEF patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We analysed HFrEF patients on sub\u2010optimal doses of ACEI\/ARB and\/or beta\u2010blockers from the BIOSTAT\u2010CHF study stratified by age. Patients underwent a 3\u2010month up\u2010titration period. We used inverse probability weighting to adjust for the likelihood of successful up\u2010titration to determine the association of achieved dose with mortality and\/or heart failure hospitalisation, testing for an interaction with age. Over a median follow\u2010up of 21\u2009months in 1720 HFrEF patients (76.5% male, mean age 67\u2009years), the primary outcome occurred in 558 patients. Increased percentage of target dose of ACEI\/ARB and beta\u2010blocker achieved at 3\u00a0months were both significantly associated with reduced incidence of the primary outcome, [ACEI\u2010ARB: hazard ratio (HR) per 12.5% increase in dose: 0.92, 95% confidence interval (CI) 0.91\u20130.94,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001; beta\u2010blocker: HR 0.98, 95% CI 0.95\u20131.00,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.046], with a significant interaction with age seen for beta\u2010blockers but not ACEI\/ARB (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.034 and\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.22, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Achieving higher doses of ACEI\/ARB was associated with improved outcome regardless of age. However, achieving higher doses of beta\u2010blockers was only associated with improved outcome in younger, but not in older patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1799","type":"journal-article","created":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T02:35:36Z","timestamp":1585190136000},"page":"436-444","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Heart failure treatment up\u2010titration and outcome and age: an analysis of BIOSTAT\u2010CHF"],"prefix":"10.1093","volume":"23","author":[{"given":"Ify R.","family":"Mordi","sequence":"first","affiliation":[{"name":"Division of Molecular and Clinical Medicine University of Dundee  Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Ouwerkerk","sequence":"additional","affiliation":[{"name":"National Heart Centre Singapore  Singapore"},{"name":"Department of Dermatology, Amsterdam UMC University of Amsterdam, Amsterdam Infection &amp; Immunity Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK) Berlin Institute of Health Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin; Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Cleland","sequence":"additional","affiliation":[{"name":"National Heart &amp; Lung Institute Royal Brompton &amp; Harefield Hospitals, Imperial College  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Dickstein","sequence":"additional","affiliation":[{"name":"University of Bergen  Bergen Norway"},{"name":"Stavanger University Hospital  Stavanger 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