{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:41:39Z","timestamp":1790700099711,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T00:00:00Z","timestamp":1625788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007605","name":"Aarhus University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007605","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Using Scandinavian population-based registries, we assessed risk of stroke\/systemic embolism (SE) and bleeding with non-vitamin K antagonist oral anticoagulants compared with warfarin in anticoagulation-na\u00efve patients with atrial fibrillation (AF).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>This historical cohort study included 219\u00a0545 AF patients [median age 74 years; 43% women; mean CHA2DS2-VASc (congestive heart failure, hypertension, age \u226575 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, age 65\u201374 years, sex category) score 3.3] initiating apixaban, dabigatran, rivaroxaban, or warfarin in Denmark, Norway, and Sweden (1 January 2013 to 31 December 2016). The primary endpoints were stroke\/SE and major bleeding. The median follow-up times were 9.7 (3.9\u201321.5) months for stroke\/SE and 9.6 (3.8\u201321.3) months for bleeding. Apixaban and warfarin initiators were older and had higher CHA2DS2-VASc scores compared with dabigatran and rivaroxaban initiators. After 1:1 propensity score matching, three cohorts were created: apixaban\u2013warfarin (n\u00a0=\u00a0111\u00a0162), dabigatran\u2013warfarin (n\u00a0=\u00a056\u00a0856), and rivaroxaban\u2013warfarin (n\u00a0=\u00a061\u00a0198). Adjusted hazard ratios (HRs) were estimated using a Cox regression. For stroke\/SE, adjusted HRs against warfarin were 0.96 [95% confidence interval (CI): 0.87\u20131.06] for apixaban, 0.89 (95% CI: 0.80\u20131.00) for dabigatran, and 1.03 (95% CI: 0.92\u20131.14) for rivaroxaban. For major bleeding, the HRs against warfarin were 0.73 (95% CI: 0.67\u20130.78) for apixaban, 0.89 (95% CI: 0.82\u20130.97) for dabigatran, and 1.15 (95% CI: 1.07\u20131.25) for rivaroxaban. The results in the dabigatran cohort did not hold in all dose-defined subgroups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In this large Scandinavian study among AF patients initiating oral anticoagulation, those initiating dabigatran, apixaban, and rivaroxaban had similar rates of stroke\/SE to patients initiating warfarin. Rates of major bleeding were lower with apixaban and dabigatran and higher with rivaroxaban, each compared with warfarin.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjqcco\/qcab048","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T19:47:43Z","timestamp":1625687263000},"page":"577-587","source":"Crossref","is-referenced-by-count":18,"title":["Effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in atrial fibrillation: a Scandinavian population-based cohort study"],"prefix":"10.1093","volume":"8","author":[{"given":"Sigrun","family":"Halvorsen","sequence":"first","affiliation":[{"name":"Department of Cardiology, Oslo University Hospital Ullev\u00e5l , PO Box 4956, Nydalen, NO-0424 Oslo , Norway"},{"name":"Institute of Clinical Medicine, University of Oslo , Oslo , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren P","family":"Johnsen","sequence":"additional","affiliation":[{"name":"Danish Center for Clinical Health Services Research, Department of Clinical Medicine, Aalborg University , Aalborg , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Linder","sequence":"additional","affiliation":[{"name":"Centre for Pharmacoepidemiology, Karolinska Institutet , Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7561-7644","authenticated-orcid":false,"given":"Gerhard","family":"Sulo","sequence":"additional","affiliation":[{"name":"Centre for Disease Burden, Norwegian Institute of Public Health , Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed","family":"Ghanima","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo , Oslo , Norway"},{"name":"\u00d8stfold Hospital Trust , Kalnes , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Gislason","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte , 2900 Hellerup , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H","family":"Hohnloser","sequence":"additional","affiliation":[{"name":"Department of Cardiology, J.W. Goethe University , Frankfurt , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Pfizer Ltd , Tadworth , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faris","family":"Al-Khalili","sequence":"additional","affiliation":[{"name":"Heart, Lung and Allergy Clinic, Sophiahemmet Hospital , Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grethe S","family":"Tell","sequence":"additional","affiliation":[{"name":"Department of Global Public Health and Primary Care, University of Bergen , Bergen , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Ehrenstein","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Aarhus University Hospital , Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"key":"2022081709511957900_bib1","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1093\/eurheartj\/ehw210","article-title":"2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS","volume":"37","author":"Kirchhof","year":"2016","journal-title":"Eur Heart J"},{"key":"2022081709511957900_bib2","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jacc.2019.01.011","article-title":"2019 AHA\/ACC\/HRS focused update of the 2014 AHA\/ACC\/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society","volume":"74","author":"January","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"2022081709511957900_bib3","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","article-title":"2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the Task Force for the Diagnosis and Management of Atrial Fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC","volume":"42","author":"Hindricks","year":"2021","journal-title":"Eur Heart J"},{"key":"2022081709511957900_bib4","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1056\/NEJMoa1107039","article-title":"Apixaban versus warfarin in patients with atrial fibrillation","volume":"365","author":"Granger","year":"2011","journal-title":"N Engl J Med"},{"key":"2022081709511957900_bib5","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1056\/NEJMoa0905561","article-title":"Dabigatran versus warfarin in patients with atrial fibrillation","volume":"361","author":"Connolly","year":"2009","journal-title":"N Engl J Med"},{"key":"2022081709511957900_bib6","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1009638","article-title":"Rivaroxaban versus warfarin in nonvalvular atrial fibrillation","volume":"365","author":"Patel","year":"2011","journal-title":"N Engl J Med"},{"key":"2022081709511957900_bib7","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1056\/NEJMoa1310907","article-title":"Edoxaban versus warfarin in patients with atrial fibrillation","volume":"369","author":"Giugliano","year":"2013","journal-title":"N Engl J Med"},{"key":"2022081709511957900_bib8","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0140-6736(13)62343-0","article-title":"Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials","volume":"383","author":"Ruff","year":"2014","journal-title":"Lancet"},{"key":"2022081709511957900_bib9","doi-asserted-by":"crossref","first-page":"e003725","DOI":"10.1161\/JAHA.116.003725","article-title":"Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation","volume":"5","author":"Yao","year":"2016","journal-title":"J Am Heart Assoc"},{"key":"2022081709511957900_bib10","doi-asserted-by":"crossref","first-page":"i3189","DOI":"10.1136\/bmj.i3189","article-title":"Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study","volume":"353","author":"Larsen","year":"2016","journal-title":"BMJ"},{"key":"2022081709511957900_bib11","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.1161\/STROKEAHA.118.020232","article-title":"Effectiveness and safety of oral anticoagulants among nonvalvular atrial fibrillation patients","volume":"49","author":"Lip","year":"2018","journal-title":"Stroke"},{"key":"2022081709511957900_bib12","doi-asserted-by":"crossref","first-page":"e0221500","DOI":"10.1371\/journal.pone.0221500","article-title":"Comparative effectiveness of warfarin, dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation: a nationwide pharmacoepidemiological study","volume":"14","author":"Kjerpeseth","year":"2019","journal-title":"PLoS One"},{"key":"2022081709511957900_bib13","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1160\/TH16-08-0658","article-title":"\u201cUnreal world\u201d or \u201creal world\u201d data in oral anticoagulant treatment of atrial fibrillation","volume":"116","author":"Freedman","year":"2016","journal-title":"Thromb Haemost"},{"key":"2022081709511957900_bib14","doi-asserted-by":"crossref","first-page":"563","DOI":"10.2147\/CLEP.S179083","article-title":"The Danish health care system and epidemiological research: from health care contacts to database records","volume":"11","author":"Schmidt","year":"2019","journal-title":"Clin Epidemiol"},{"key":"2022081709511957900_bib15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1177\/1403494819859737","article-title":"The Norwegian Patient Registry and the Norwegian Registry for Primary Health Care: research potential of two nationwide health-care registries","volume":"48","author":"Bakken","year":"2020","journal-title":"Scand J Public Health"},{"key":"2022081709511957900_bib16","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s10654-009-9350-y","article-title":"The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research","volume":"24","author":"Ludvigsson","year":"2009","journal-title":"Eur J Epidemiol"},{"key":"2022081709511957900_bib17","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1160\/TH14-10-0859","article-title":"Safety and efficacy of well managed warfarin: a report from the Swedish quality register Auricula","volume":"113","author":"Sj\u00f6gren","year":"2015","journal-title":"Thromb Haemost"},{"key":"2022081709511957900_bib18","first-page":"A5010","article-title":"Good quality of oral anticoagulation treatment in general practice using international normalised ratio point of care testing","volume":"62","author":"L\u00f8kkegaard","year":"2015","journal-title":"Dan Med J"},{"key":"2022081709511957900_bib19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1093\/ehjcvp\/pvw031","article-title":"A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants","volume":"3","author":"Halvorsen","year":"2017","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"2022081709511957900_bib20","doi-asserted-by":"crossref","first-page":"e000682","DOI":"10.1136\/openhrt-2017-000682","article-title":"Efficacy and safety of non-vitamin K antagonist oral anticoagulants compared with warfarin in patients with atrial fibrillation","volume":"4","author":"Friberg","year":"2017","journal-title":"Open Heart"},{"key":"2022081709511957900_bib21","volume-title":"ICD-10: International Statistical Classification of Diseases and Related Health Problems","author":"World Health Organization","year":"2004","edition":"2nd ed."},{"key":"2022081709511957900_bib22","article-title":"NOMESCO classification of surgical procedures (NCSP), version 1.16","author":"Nordic Co-operation","year":"2011"},{"key":"2022081709511957900_bib23","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1600-0404.2010.01402.x","article-title":"Validation of the Swedish inpatient and cause-of-death registers in the context of stroke","volume":"123","author":"Appelros","year":"2011","journal-title":"Acta Neurol Scand"},{"key":"2022081709511957900_bib24","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/pds.3457","article-title":"The Nordic prescription databases as a resource for pharmacoepidemiological research\u2014a literature review","volume":"22","author":"Wettermark","year":"2013","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2022081709511957900_bib25","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1186\/1471-2458-11-450","article-title":"External review and validation of the Swedish national inpatient register","volume":"11","author":"Ludvigsson","year":"2011","journal-title":"BMC Public Health"},{"key":"2022081709511957900_bib26","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1177\/1403494819859737","article-title":"The Norwegian Patient Registry and the Norwegian Registry for Primary Health Care: research potential of two nationwide health-care registries","volume":"48","author":"Bakken","year":"2020","journal-title":"Scand J Public Health"},{"key":"2022081709511957900_bib27","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3109\/14017431.2012.673728","article-title":"Validity of the diagnoses atrial fibrillation and atrial flutter in a Danish patient registry","volume":"46","author":"Rix","year":"2012","journal-title":"Scand Cardiovasc J"},{"key":"2022081709511957900_bib28","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2147\/CLEP.S103346","article-title":"Validation of self-reported and hospital-diagnosed atrial fibrillation: the HUNT study","volume":"8","author":"Malmo","year":"2016","journal-title":"Clin Epidemiol"},{"key":"2022081709511957900_bib29","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s10654-009-9404-1","article-title":"Atrial fibrillation in the Malmo Diet and Cancer Study: a study of occurrence, risk factors and diagnostic validity","volume":"25","author":"Smith","year":"2010","journal-title":"Eur J Epidemiol"},{"key":"2022081709511957900_bib30","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/pst.433","article-title":"Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies","volume":"10","author":"Austin","year":"2011","journal-title":"Pharm Stat"},{"key":"2022081709511957900_bib31","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1002\/pds.4217","article-title":"Estimating medication stopping fraction and real-time prevalence of drug use in pharmaco-epidemiologic databases: an application of the reverse waiting time distribution","volume":"26","author":"St\u00f8vring","year":"2017","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2022081709511957900_bib32","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1002\/pds.4114","article-title":"Determining prescription durations based on the parametric waiting time distribution","volume":"25","author":"St\u00f8vring","year":"2016","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2022081709511957900_bib33","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2147\/CLEP.S91125","article-title":"The Danish National Patient Registry: a review of content, data quality, and research potential","volume":"7","author":"Schmidt","year":"2015","journal-title":"Clin Epidemiol"},{"key":"2022081709511957900_bib34","doi-asserted-by":"crossref","first-page":"e012832","DOI":"10.1136\/bmjopen-2016-012832","article-title":"Positive predictive value of cardiovascular diagnoses in the Danish National Patient Registry: a validation study","volume":"6","author":"Sundb\u00f8ll","year":"2016","journal-title":"BMJ Open"},{"key":"2022081709511957900_bib35","doi-asserted-by":"crossref","first-page":"563","DOI":"10.2147\/CLEP.S179083","article-title":"The Danish healthcare system and epidemiological research: from healthcare contacts to database records","volume":"11","author":"Schmidt","year":"2019","journal-title":"Clin Epidemiol"},{"key":"2022081709511957900_bib36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/europace\/euu225","article-title":"Non-vitamin K antagonist oral anticoagulation agents in anticoagulant na\u00efve atrial fibrillation patients: Danish nationwide descriptive data 2011\u20132013","volume":"17","author":"Olesen","year":"2015","journal-title":"Europace"},{"key":"2022081709511957900_bib37","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1007\/s00228-017-2296-1","article-title":"Trends in use of warfarin and direct oral anticoagulants in atrial fibrillation in Norway, 2010 to 2015","volume":"73","author":"Kjerpeseth","year":"2017","journal-title":"Eur J Clin Pharmacol"},{"key":"2022081709511957900_bib38","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.1161\/STROKEAHA.117.017549","article-title":"Real-world setting comparison of nonvitamin-K antagonist oral anticoagulants versus vitamin-K antagonists for stroke prevention in atrial fibrillation: a systematic review and meta-analysis","volume":"48","author":"Ntaios","year":"2017","journal-title":"Stroke"},{"key":"2022081709511957900_bib39","first-page":"907","article-title":"Ischaemic and haemorrhagic stroke associated with non-vitamin K antagonist oral anticoagulants and warfarin use in patients with atrial fibrillation: a nationwide cohort study","volume":"38","author":"Staerk","year":"2017","journal-title":"Eur Heart J"},{"key":"2022081709511957900_bib40","doi-asserted-by":"crossref","first-page":"e004517","DOI":"10.1161\/JAHA.116.004517","article-title":"Major bleeding complications and persistence with oral anticoagulation in non-valvular atrial fibrillation: contemporary findings in real-life Danish patients","volume":"6","author":"Lamberts","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"2022081709511957900_bib41","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/ehjcvp\/pvz086","article-title":"Comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in atrial fibrillation: a nationwide cohort study","volume":"6","author":"Rutherford","year":"2020","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"2022081709511957900_bib42","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1093\/eurheartj\/ehs253","article-title":"2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation developed with the special contribution of the European Heart Rhythm Association","volume":"33","author":"Camm","year":"2012","journal-title":"Eur Heart J"}],"container-title":["European Heart Journal - Quality of Care and Clinical Outcomes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ehjqcco\/advance-article-pdf\/doi\/10.1093\/ehjqcco\/qcab048\/39539831\/qcab048.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjqcco\/article-pdf\/8\/5\/577\/45450228\/qcab048.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjqcco\/article-pdf\/8\/5\/577\/45450228\/qcab048.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T09:52:25Z","timestamp":1660729945000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ehjqcco\/article\/8\/5\/577\/6318368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,9]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,7,9]]},"published-print":{"date-parts":[[2022,8,17]]}},"URL":"https:\/\/doi.org\/10.1093\/ehjqcco\/qcab048","relation":{},"ISSN":["2058-5225","2058-1742"],"issn-type":[{"value":"2058-5225","type":"print"},{"value":"2058-1742","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9]]},"published":{"date-parts":[[2021,7,9]]}}}