{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:22:02Z","timestamp":1790076122319,"version":"4.0.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":1119,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Research Council of Norway","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Novartis Norway AS"},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We aimed to study initiation, adherence, and long-term persistence to beta-blockers (BB), renin\u2013angiotensin system inhibitors (RASi), and mineralocorticoid receptor antagonists (MRA) in a nationwide cohort of patients with heart failure (HF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients aged 18\u201380 years in Norway with a first diagnosis of HF from 2014 until 2020 that survived \u226530 days were identified from the Norwegian Patient Registry and linked to the Norwegian Prescription Database. We collected information about BB, RASi [angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and angiotensin receptor-neprilysin inhibitors (ARNI)], and MRA. Dual HF therapy was defined as taking at least two out of three drug classes, whereas triple HF therapy was defined as taking all three. Initiation (time to initiation) and persistence (time to discontinuation using a grace period of 30 days) of HF drugs was calculated by the Kaplan\u2013Meier method, followed to outcome of interest, death, or December 2020. One-year adherence was measured as proportion of days covered (PDC) using a cut-off at 80%. For adherence and persistence measurements, we allowed for maximum 60 days of stockpiling and switching within drug groups. We performed sensitivity analyses to test the robustness of our findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Out of 54\u2009899 patients included in the cohort, 75%, 69%, and 21% initiated a BB, RASi, and MRA, respectively, whereas 13% did not receive any. Dual and triple HF therapy was prescribed to 61% and 16%, respectively. The proportion of adherent patients during the first year following initiation was 83%, 81%, 84%, and 61% for BB, RASi, ARNI, and MRA, whereas 42% and 5% were adherent to dual and triple HF therapy, respectively. From 2 to 5 years following initiation, persistence decreased from 58% to 38%, 57% to 37%, and 31% to 15% for BB, RASi, and MRA, respectively. Within the RASi group, persistence was higher for ARNI than for ACEI and ARB. There were no major changes in either initiation or adherence of the drug classes from 2014 to 2019, except for an increase in initiation and adherence of MRA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We found low adherence to dual and triple HF therapies in this nationwide cohort study of newly diagnosed HF patients. Efforts are needed to increase adherence and persistence to HF therapies into clinical practice, emphasizing maintenance of multiple drug therapies in patients with such an indication.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14206","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T01:40:05Z","timestamp":1666316405000},"page":"405-415","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Adherence and Persistence to Pharmacotherapy in Patients with Heart Failure: A Nationwide Cohort Study, 2014\u20132020"],"prefix":"10.1093","volume":"10","author":[{"given":"Kristina Malene","family":"\u00d8degaard","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo , Oslo ,","place":["Norway"]},{"name":"Novartis Norway AS , Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandre Svatun","family":"Lirhus","sequence":"additional","affiliation":[{"name":"Institute of Health and Society, University of Oslo , Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Olav","family":"Melberg","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, UiT - The Arctic University of Norway , Troms\u00f8 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Hall\u00e9n","sequence":"additional","affiliation":[{"name":"Arxx Therapeutics , Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrun","family":"Halvorsen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo , Oslo ,","place":["Norway"]},{"name":"Department of Cardiology, Oslo University Hospital Ulleval , Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"2026012114121722000_ehf214206-bib-0001","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1016\/S0140-6736(17)31071-1","article-title":"Heart failure","volume":"390","author":"Metra","year":"2017","journal-title":"Lancet (London, England)"},{"key":"2026012114121722000_ehf214206-bib-0002","doi-asserted-by":"crossref","DOI":"10.1038\/s41572-020-0151-7","article-title":"Acute heart failure","volume":"6","author":"Arrigo","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"2026012114121722000_ehf214206-bib-0003","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/ejhf.2333","article-title":"2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"24","author":"McDonagh","year":"2022","journal-title":"Eur J Heart Fail"},{"key":"2026012114121722000_ehf214206-bib-0004","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/j.1524-4733.2007.00213.x","article-title":"Medication compliance and persistence: Terminology and definitions","volume":"11","author":"Cramer","year":"2008","journal-title":"Value Health"},{"key":"2026012114121722000_ehf214206-bib-0005","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1002\/pds.4868","article-title":"Adherence to ESC guideline-recommended medications over a 36-month follow-up period after hospitalization for heart failure: Results from the EPICAL2 cohort study","volume":"28","author":"Bitar","year":"2019","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2026012114121722000_ehf214206-bib-0006","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1161\/CIRCULATIONAHA.106.669101","article-title":"Persistent use of evidence-based pharmacotherapy in heart failure is associated with improved outcomes","volume":"116","author":"Gislason","year":"2007","journal-title":"Circulation"},{"key":"2026012114121722000_ehf214206-bib-0007","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/phar.2107","article-title":"Association between medication adherence and the outcomes of heart failure","volume":"38","author":"Hood","year":"2018","journal-title":"Pharmacotherapy"},{"key":"2026012114121722000_ehf214206-bib-0008","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1002\/ejhf.2271","article-title":"Heart failure drug titration, discontinuation, mortality and heart failure hospitalization risk: A multinational observational study (US, UK and Sweden)","volume":"23","author":"Savarese","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"2026012114121722000_ehf214206-bib-0009","doi-asserted-by":"crossref","DOI":"10.1186\/s12872-022-02522-y","article-title":"A nationwide registry study on heart failure in Norway from 2008 to 2018: Variations in lookback period affect incidence estimates","volume":"22","author":"\u00d8degaard","year":"2022","journal-title":"BMC Cardiovasc Disord"},{"key":"2026012114121722000_ehf214206-bib-0010","volume-title":"Hurtig metodevurdering sakubitril\/valsartan til behandling av HFrEF","author":"Statens legemiddelverk (Norwegian Medicines Agency)","year":"2018"},{"key":"2026012114121722000_ehf214206-bib-0011","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1185\/03007990903126833","article-title":"Good and poor adherence: Optimal cut-point for adherence measures using administrative claims data","volume":"25","author":"Karve","year":"2009","journal-title":"Curr Med Res Opin"},{"key":"2026012114121722000_ehf214206-bib-0012","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1345\/aph.1L496","article-title":"Comparison of methods to assess medication adherence and classify nonadherence","volume":"43","author":"Hansen","year":"2009","journal-title":"Ann Pharmacother"},{"key":"2026012114121722000_ehf214206-bib-0013","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1161\/CIRCOUTCOMES.108.813600","article-title":"Changes in adherence to evidence-based medications in the first year after initial hospitalization for heart failure: Observational cohort study from 1994 to 2003","volume":"2","author":"Lamb","year":"2009","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"2026012114121722000_ehf214206-bib-0014","first-page":"609","article-title":"Compliance, persistence, and switching patterns for ACE inhibitors and ARBs","volume":"17","author":"Vegter","year":"2011","journal-title":"Am J Manag Care"},{"key":"2026012114121722000_ehf214206-bib-0015","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s11096-013-9891-8","article-title":"A method for calculating adherence to polypharmacy from dispensing data records","volume":"36","author":"Arnet","year":"2014","journal-title":"Int J Clin Pharm"},{"key":"2026012114121722000_ehf214206-bib-0016","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/clpt.2011.228","article-title":"Comparisons of persistence and durability among three oral antidiabetic therapies using electronic prescription-fill data: The impact of adherence requirements and stockpiling","volume":"90","author":"Greevy","year":"2011","journal-title":"Clin Pharmacol Ther"},{"key":"2026012114121722000_ehf214206-bib-0017","volume-title":"HELFO","author":"The Norwegian Health Economics Administration"},{"key":"2026012114121722000_ehf214206-bib-0018","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.pcad.2013.02.001","article-title":"Adherence to cardiovascular medications: Lessons learned and future directions","volume":"55","author":"Kronish","year":"2013","journal-title":"Prog Cardiovasc Dis"},{"key":"2026012114121722000_ehf214206-bib-0019","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s40256-019-00367-z","article-title":"Adherence to disease-modifying therapy in patients hospitalized for HF: Findings from a community-based study","volume":"20","author":"Spreafico","year":"2020","journal-title":"Am J Cardiovasc Drugs"},{"key":"2026012114121722000_ehf214206-bib-0020","first-page":"561","article-title":"Treatment initiation patterns, modifications, and medication adherence among newly diagnosed heart failure patients: A retrospective claims database analysis","volume":"22","author":"Deschaseaux","year":"2016","journal-title":"J Manag Care Spec Pharm"},{"key":"2026012114121722000_ehf214206-bib-0021","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ijcard.2021.02.016","article-title":"Treatment prescription, adherence, and persistence after the first hospitalization for heart failure: A population-based retrospective study on 100785 patients","volume":"330","author":"Scalvini","year":"2021","journal-title":"Int J Cardiol"},{"key":"2026012114121722000_ehf214206-bib-0022","article-title":"Completeness and correctness of acute myocardial infarction diagnoses in a medical quality register and an administrative health register","author":"Govatsmark","year":"2018","journal-title":"Scand J Public Health"},{"key":"2026012114121722000_ehf214206-bib-0023","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1177\/1403494815621641","article-title":"Comparison of the validity of stroke diagnoses in a medical quality register and an administrative health register","volume":"44","author":"Varmdal","year":"2016","journal-title":"Scand J Public Health"},{"key":"2026012114121722000_ehf214206-bib-0024","article-title":"Validity of heart failure diagnoses in administrative databases: A systematic review and meta-analysis","volume":"9","author":"McCormick","year":"2014","journal-title":"PLoS ONE"},{"key":"2026012114121722000_ehf214206-bib-0025","doi-asserted-by":"crossref","first-page":"589","DOI":"10.2147\/CLEP.S251710","article-title":"Identification of patients with new-onset heart failure and reduced ejection fraction in Danish administrative registers","volume":"12","author":"Madelaire","year":"2020","journal-title":"Clin Epidemiol"},{"key":"2026012114121722000_ehf214206-bib-0026","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","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":"18","author":"Ponikowski","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2026012114121722000_ehf214206-bib-0027","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1093\/ehjcvp\/pvaa097","article-title":"Patient-reported outcomes and medication adherence in patients with heart failure","volume":"7","author":"Rasmussen","year":"2020","journal-title":"Eur Heart J - Cardiovasc Pharmacother"},{"key":"2026012114121722000_ehf214206-bib-0028","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":"2026012114121722000_ehf214206-bib-0029","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1345\/aph.1H018","article-title":"Measurement of adherence in pharmacy administrative databases: a proposal for standard definitions and preferred measures","volume":"40","author":"Hess","year":"2006","journal-title":"Ann Pharmacother"},{"key":"2026012114121722000_ehf214206-bib-0030","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s10741-017-9656-x","article-title":"In search of a standard when analyzing medication adherence in patients with heart failure using claims data: A systematic review","volume":"23","author":"Krueger","year":"2018","journal-title":"Heart Fail Rev"},{"key":"2026012114121722000_ehf214206-bib-0031","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1097\/MLR.0b013e31829b1d2a","article-title":"Standardizing terminology and definitions of medication adherence and persistence in research employing electronic databases","volume":"51","author":"Raebel","year":"2013","journal-title":"Med Care"},{"key":"2026012114121722000_ehf214206-bib-0032","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.ijcard.2016.06.263","article-title":"Medication adherence and persistence according to different antihypertensive drug classes: A retrospective cohort study of 255,500 patients","volume":"220","author":"Schulz","year":"2016","journal-title":"Int J Cardiol"},{"key":"2026012114121722000_ehf214206-bib-0033","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/cpt.1378","article-title":"Comparison of different strategies to measure medication adherence via claims data in patients with chronic heart failure","volume":"106","author":"Ihle","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"2026012114121722000_ehf214206-bib-0034","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1002\/ejhf.2149","article-title":"Rapid evidence-based sequencing of foundational drugs for heart failure and a reduced ejection fraction","volume":"23","author":"Packer","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"2026012114121722000_ehf214206-bib-0035","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1016\/j.jacc.2022.03.351","article-title":"Underutilization of guideline-directed medical therapy in heart failure","volume":"79","author":"Spall","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"2026012114121722000_ehf214206-bib-0036","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1002\/ejhf.2378","article-title":"Navigating between Scylla and Charybdis: Challenges and strategies for implementing guideline-directed medical therapy in heart failure with reduced ejection fraction","volume":"23","author":"Seferovi\u0107","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"2026012114121722000_ehf214206-bib-0037","first-page":"442","article-title":"Guideline-directed medical therapy clinics: A call to action for the heart failure team","volume":"7","author":"O'Connor","year":"2019","journal-title":"JACC: Heart Failure"},{"key":"2026012114121722000_ehf214206-bib-0038","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002528","article-title":"A clinical decision support tool for improving adherence to guidelines on anticoagulant therapy in patients with atrial fibrillation at risk of stroke: A cluster-randomized trial in a Swedish primary care setting (the CDS-AF study)","volume":"15","author":"Karlsson","year":"2018","journal-title":"PLoS Med"},{"key":"2026012114121722000_ehf214206-bib-0039","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1016\/j.jacc.2022.03.338","article-title":"Electronic alerts to improve heart failure therapy in outpatient practice: A cluster randomized trial","volume":"79","author":"Ghazi","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"2026012114121722000_ehf214206-bib-0040","doi-asserted-by":"crossref","DOI":"10.2196\/32554","article-title":"A smartphone-based model of care to support patients with cardiac disease transitioning from hospital to the community (TeleClinical care): Pilot randomized controlled trial","volume":"10","author":"Indraratna","year":"2022","journal-title":"JMIR Mhealth Uhealth"},{"key":"2026012114121722000_ehf214206-bib-0041","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/S0140-6736(18)31880-4","article-title":"Efficacy of telemedical interventional management in patients with heart failure (TIM-HF2): A randomised, controlled, parallel-group, unmasked trial","volume":"392","author":"Koehler","year":"2018","journal-title":"Lancet (London, England)"},{"key":"2026012114121722000_ehf214206-bib-0042","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/ehf2.13748","article-title":"Real-world evidence in a national health service: Results of the UK CardioMEMS HF system post-market study","volume":"9","author":"Cowie","year":"2022","journal-title":"ESC Heart Fail"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ehf2.14206","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ehf2.14206","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/10\/1\/405\/65108184\/eschf_10_1_405.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/10\/1\/405\/65108184\/eschf_10_1_405.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T19:13:49Z","timestamp":1769022829000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/10\/1\/405\/8304960"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,10,20]]},"published-print":{"date-parts":[[2023,2,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.14206","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,2]]},"published":{"date-parts":[[2022,10,20]]},"assertion":[{"value":"2022-04-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}