{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T13:33:31Z","timestamp":1794317611133,"version":"4.9.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,11,5]],"date-time":"2019-11-05T00:00:00Z","timestamp":1572912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Daiichi Sankyo Pharma Development"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Non-vitamin K antagonist oral anticoagulants represent a new option for prevention of embolic events in patients with atrial fibrillation (AF). However, little is known about the impact of non-cardiac comorbidities on the efficacy and safety profile of these drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In a post hoc analysis of the ENGAGE AF-TIMI 48 trial, we analysed 21\u00a0105 patients with AF followed for an average of 2.8\u2009years and randomized to either a higher-dose edoxaban regimen (HDER), a lower-dose edoxaban regimen, or warfarin. We used the updated Charlson Comorbidity Index (CCI) to stratify the patients according to the burden of concomitant disease (CCI\u2009=\u20090, 1, 2, 3, and \u22654). The treatment groups were then compared for safety, efficacy, and net clinical outcomes across CCI categories. There were 32.0%, 7.3%, 42.1%, 12.7%, and 6.0% of patients with CCI scores of 0, 1, 2, 3, and \u22654, respectively. A CCI score \u22654 was associated with significantly higher rates of thromboembolic events, bleeding, and death compared to CCI\u2009=\u20090 (P\u2009&amp;lt;\u20090.05 for each). The annualized rates of the primary net clinical outcome (stroke\/systemic embolism, major bleeding, or death) for CCI\u2009=\u20090, 1, 2, 3, or \u22654 were 5.9%, 8.7%, 6.6%, 10.3%, and 13.6% (Ptrend &amp;lt; 0.001). There were no significant interactions between treatment with HDER vs. warfarin and efficacy, safety, and net outcomes across the CCI groups (P-interaction &amp;gt; 0.10 for each).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion\u2003<\/jats:title>\n                    <jats:p>Although increasing CCI scores are associated with worse outcomes, the efficacy, safety, and net clinical outcomes of edoxaban vs. warfarin were independent of the degree of comorbidity present.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjcvp\/pvz061","type":"journal-article","created":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T08:11:50Z","timestamp":1572423110000},"page":"167-175","source":"Crossref","is-referenced-by-count":21,"title":["Efficacy and safety of edoxaban compared with warfarin according to the burden of diseases in patients with atrial fibrillation: insights from the ENGAGE AF-TIMI 48 trial"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0633-3853","authenticated-orcid":false,"given":"Andr\u00e9 M","family":"Nicolau","sequence":"first","affiliation":[{"name":"Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, Rua Botucatu, 720 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Corbalan","sequence":"additional","affiliation":[{"name":"Hospital Clinico Pontificia Universidad Catolica de Chile, Facultad de Medicina, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose C","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Departamento de Cardiopneumologia, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian T","family":"Ruff","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Hale Building, Room 7022, 60 Fenwood Road, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Zierhut","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Europe GmbH, Medical Affairs Antithrombotic & Cardiovascular Therapeutic Area, Zielstattstra\u00dfe 48, 81379 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kerschnitzki","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Europe GmbH, Medical Affairs Antithrombotic & Cardiovascular Therapeutic Area, Zielstattstra\u00dfe 48, 81379 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor","family":"Duris","sequence":"additional","affiliation":[{"name":"Fakultn\u00e1 nemocnica s poliklinikou, Nov\u00e9 Z\u00e1mky, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen","family":"Juul-M\u00f6ller","sequence":"additional","affiliation":[{"name":"Sk\u00e5ne University Hospital (SUS), Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juri","family":"Voitk","sequence":"additional","affiliation":[{"name":"Department of Invasive Cardiology, Center of Cardiology, North Estonia Medical Center Foundation, J. S\u00fctiste tee 19, 13419 Tallinn, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Trevisan","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Nordio","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Hale Building, Room 7022, 60 Fenwood Road, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott M","family":"Antman","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Hale Building, Room 7022, 60 Fenwood Road, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P","family":"Giugliano","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Hale Building, Room 7022, 60 Fenwood Road, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,5]]},"reference":[{"key":"2020090710540049700_pvz061-B1","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1093\/eurheartj\/ehi825","article-title":"Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study","volume":"27","author":"Heeringa","year":"2006","journal-title":"Eur Heart J"},{"key":"2020090710540049700_pvz061-B2","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1001\/jama.285.18.2370","article-title":"Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm 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