{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:20:22Z","timestamp":1792200022527,"version":"4.4.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"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":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Use and dosing of guideline\u2010directed medical therapy (GDMT) in patients with heart failure (HF) have been shown to be suboptimal. Among new users of GDMT in HF, we followed the real\u2010life patterns of dose titration and discontinuation of angiotensin\u2010converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), beta\u2010blockers, mineralocorticoid receptor antagonists (MRA) and angiotensin receptor\u2013neprilysin inhibitors (ARNI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      New users were identified in health care databases in Sweden, UK and US between 2016\u20132019. Inclusion criterion was a recent HF hospitalization (HHF) triggering the initiation of GDMT. Patients were grouped by GDMT, i.e. ACEi, ARB, beta\u2010blocker, MRA and ARNI, and stratified by initial dose. Follow\u2010up was 12\u2009months, until death or study end. Outcomes were dose titration within each drug class, discontinuation and first HHF or death. Dose\/discontinuation follow\u2010up was assessed daily based on the coverage length of a filled prescription and reported on day 365. New users of ACEi (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a08426), ARB (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a02303), beta\u2010blockers (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a010\u2009476), MRA (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a017\u2009421), and ARNI (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a029\u2009546) were identified. Over 12\u2009months, target dose achievement was 15%, 10%, 12%, 30%, and discontinuation was 55%, 33%, 24% and 27% for ACEi, ARB, beta\u2010blockers and ARNI, respectively. MRA was rarely titrated and discontinuation rates were high (40%). Event rates for HHF or death ranged from 40.0\u201386.9 per 100 patient\u2010years across the treatment groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Despite high risk of clinical events following HHF, new initiation of GDMT was followed by consistent patterns of low up\u2010titration and early GDMT discontinuation in three countries with different health care and economies. Our data highlight the urgent need for moving away from long sequential approach when initiating HF treatment and for improving just\u2010in\u2010time decision support for patients and health care providers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2271","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T01:10:12Z","timestamp":1623805812000},"page":"1499-1511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":168,"title":["Heart failure drug titration, discontinuation, mortality and heart failure hospitalization risk: a multinational observational study (\n                    <scp>US<\/scp>\n                    ,\n                    <scp>UK<\/scp>\n                    and Sweden)"],"prefix":"10.1093","volume":"23","author":[{"given":"Gianluigi","family":"Savarese","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine Karolinska Institute, and Heart and Vascular Theme, Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Bodegard","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Norhammar","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Department of Medicine Solna, Karolinska Institute  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sartipy","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gothenburg Sweden"},{"name":"Systems Biology Research Center, School of Bioscience, University of Sk\u00f6vde  Sk\u00f6vde Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Thuresson","sequence":"additional","affiliation":[{"name":"Statisticon  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin R.","family":"Cowie","sequence":"additional","affiliation":[{"name":"Faculty of Lifesciences &amp; Medicine King's College London  London UK"},{"name":"Division of Guy's &amp; St Thomas' NHS Foundation Trust Royal Brompton Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg C.","family":"Fonarow","sequence":"additional","affiliation":[{"name":"Division of Cardiology, David Geffen School of Medicine University of California, Los Angeles Medical Center  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.S.","family":"Coats","sequence":"additional","affiliation":[{"name":"University of Warwick  Coventry 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