{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:49:12Z","timestamp":1782488952909,"version":"3.54.5"},"reference-count":36,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"unspecified","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["WI246683"],"award-info":[{"award-number":["WI246683"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,8,3]]},"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The risk for stroke in adults with congenital heart disease (ACHD) is increased, especially in the setting of commonly ensuing atrial arrhythmias (AA), namely atrial fibrillation, atrial flutter or intra-atrial re-entrant tachycardia. Data are limited regarding treatment with non-vitamin K oral anticoagulants in long-term studies involving patients with ACHD and AA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>PReventiOn of ThromboEmbolism in Adults with Congenital Hear\u03a4 disease and Atrial aRrhythmias is a prospective, multicenter, single-arm, non-interventional cohort study designed to investigate the safety and efficacy of apixaban for the prevention of thromboembolism in ACHD with AA in a \u2018real-world\u2019 setting. Eligible patients will be evaluated by the means of available registries and clinical counter. The study aims to accumulate approximately 500 patient-years of exposure to apixaban as part of routine care. Enrolment will take place at four ACHD centres in Greece. The first patient was enrolled in July 2019. The primary efficacy endpoint is a composite of stroke, systemic or pulmonary embolism and intracardiac thrombosis. The primary safety endpoint is major bleeding, according to the International Society on Thrombosis and Haemostasis bleeding criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study protocol has been approved by the institutional review board\/independent ethics committee at each site prior to study commencement. All patients will provide written informed consent. Results will be disseminated at scientific meetings and published in peer-reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT03854149\">NCT03854149<\/jats:ext-link>\n                      ; Pre-results.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-038012","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T19:24:38Z","timestamp":1600802678000},"page":"e038012","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Rationale and design of a prospective, observational, multicentre study on the safety and efficacy of apixaban for the prevention of thromboembolism in adults with congenital heart disease and atrial arrhythmias: the PROTECT-AR study"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct03854149","registry":"10.18810\/clinical-trials-gov","type":"preResults"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1170-9133","authenticated-orcid":false,"given":"Anastasios","family":"Kartas","sequence":"first","affiliation":[{"name":"Cardiology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Doundoulakis","sequence":"additional","affiliation":[{"name":"Cardiology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despoina","family":"Ntiloudi","sequence":"additional","affiliation":[{"name":"Cardiology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Koutsakis","sequence":"additional","affiliation":[{"name":"Cardiology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diamantis","family":"Kosmidis","sequence":"additional","affiliation":[{"name":"Cardiology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Rampidis","sequence":"additional","affiliation":[{"name":"Cardiology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotiria","family":"Apostolopoulou","sequence":"additional","affiliation":[{"name":"Cardiology, Onassis Cardiac Surgery Centre, Athens, Attica, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Frogoudaki","sequence":"additional","affiliation":[{"name":"Cardiology, General University Hospital Attikon, Athens, Attica, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afrodite","family":"Tzifa","sequence":"additional","affiliation":[{"name":"Paediatric Cardiology & Adult Congenital Heart Disease, Mitera, Hygeia Group, Athens, Attica, Greece"},{"name":"Division of Biomedical Engineering and Imaging Sciences, King\u2019s College, London, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimosthenis","family":"Avramidis","sequence":"additional","affiliation":[{"name":"Paediatric Cardiology & Adult Congenital Heart Disease, Mitera, Hygeia Group, Athens, Attica, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Ntzoyvara","sequence":"additional","affiliation":[{"name":"Cardiology, Onassis Cardiac Surgery Centre, Athens, Attica, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotiria","family":"Liori","sequence":"additional","affiliation":[{"name":"Cardiology, General University Hospital Attikon, Athens, Attica, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza","family":"Mousiama","sequence":"additional","affiliation":[{"name":"Paediatric Cardiology & Adult Congenital Heart Disease, Mitera, Hygeia Group, Athens, Attica, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia Anastasia","family":"Mouratoglou","sequence":"additional","affiliation":[{"name":"Cardiology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haralambos","family":"Karvounis","sequence":"additional","affiliation":[{"name":"Cardiology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Giannakoulas","sequence":"additional","affiliation":[{"name":"Cardiology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"key":"2026062608022910000_10.9.e038012.1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2010.196147"},{"key":"2026062608022910000_10.9.e038012.2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.866319"},{"key":"2026062608022910000_10.9.e038012.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2013.12.025"},{"key":"2026062608022910000_10.9.e038012.4","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw210"},{"key":"2026062608022910000_10.9.e038012.5","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2015-308045"},{"key":"2026062608022910000_10.9.e038012.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107039"},{"key":"2026062608022910000_10.9.e038012.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2015.10.062"},{"key":"2026062608022910000_10.9.e038012.8","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s10557-017-6745-y","article-title":"Is initiating NOACs for atrial arrhythmias safe in adults with congenital heart disease?","volume":"31","author":"Yang","year":"2017","journal-title":"Cardiovasc Drugs Ther"},{"key":"2026062608022910000_10.9.e038012.9","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/chd.12627","article-title":"Anticoagulation practices in adults with congenital heart disease and atrial arrhythmias in Switzerland","volume":"13","author":"Arslani","year":"2018","journal-title":"Congenit Heart Dis"},{"key":"2026062608022910000_10.9.e038012.10","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ijcard.2019.06.014","article-title":"Non-Vitamin K antagonist oral anticoagulants (NOACs) for thromboembolic prevention, are they safe in congenital heart disease? results of a worldwide study","volume":"299","author":"Yang","year":"2020","journal-title":"Int J Cardiol"},{"key":"2026062608022910000_10.9.e038012.11","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.033502"},{"key":"2026062608022910000_10.9.e038012.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03678.x"},{"key":"2026062608022910000_10.9.e038012.13","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13140"},{"key":"2026062608022910000_10.9.e038012.14","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1056\/NEJMoa1700518","article-title":"Rivaroxaban or aspirin for extended treatment of venous thromboembolism","volume":"376","author":"Weitz","year":"2017","journal-title":"N Engl J Med Overseas Ed"},{"key":"2026062608022910000_10.9.e038012.15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1207541"},{"key":"2026062608022910000_10.9.e038012.16","doi-asserted-by":"publisher","DOI":"10.1186\/1477-9560-12-16"},{"key":"2026062608022910000_10.9.e038012.17","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200012150-00008"},{"key":"2026062608022910000_10.9.e038012.18","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ijcard.2017.07.024","article-title":"Adult congenital heart disease in Greece: preliminary data from the challenge registry","volume":"245","author":"Giannakoulas","year":"2017","journal-title":"Int J Cardiol"},{"key":"2026062608022910000_10.9.e038012.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(19)32100-X"},{"key":"2026062608022910000_10.9.e038012.20","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-1584"},{"key":"2026062608022910000_10.9.e038012.21","doi-asserted-by":"publisher","DOI":"10.1378\/chest.10-0134"},{"key":"2026062608022910000_10.9.e038012.22","doi-asserted-by":"crossref","unstructured":"Steffel J , Verhamme P , Potpara TS , et al . The 2018 European heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018:1\u201364.","DOI":"10.5603\/KP.2018.0180"},{"key":"2026062608022910000_10.9.e038012.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.02.024"},{"key":"2026062608022910000_10.9.e038012.24","first-page":"2191-4","article-title":"World Medical association Declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","year":"2013","journal-title":"JAMA"},{"key":"2026062608022910000_10.9.e038012.25","unstructured":"Aboulhosn JA , Fuller S , Bozkurt B , et al . 2018 AHA\/ACC guideline for the management of adults with congenital heart disease ACC\/AHA Task force members. J Am Coll Cardiol 2018."},{"key":"2026062608022910000_10.9.e038012.26","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.1016\/j.hrthm.2014.05.009","article-title":"PACES\/HRS expert consensus statement on the recognition and management of arrhythmias in adult congenital heart disease: developed in partnership between the pediatric and congenital electrophysiology Society (PACES) and the heart rhythm Society (HRS)","volume":"11","author":"Khairy","year":"2014","journal-title":"En Hear Rhythm"},{"key":"2026062608022910000_10.9.e038012.27","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.ijcard.2016.08.223","article-title":"Thromboprophylaxis for atrial arrhythmias in congenital heart disease: a multicenter study","volume":"223","author":"Khairy","year":"2016","journal-title":"Int J Cardiol"},{"key":"2026062608022910000_10.9.e038012.28","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/chd.12603","article-title":"Novel oral anticoagulant use in adult Fontan patients: a single center experience","volume":"13","author":"Georgekutty","year":"2018","journal-title":"Congenit Heart Dis"},{"key":"2026062608022910000_10.9.e038012.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.02.024"},{"key":"2026062608022910000_10.9.e038012.30","doi-asserted-by":"crossref","DOI":"10.3390\/jcm9061794","article-title":"Non-Vitamin K oral anticoagulants in adults with congenital heart disease: a systematic review","volume":"9","author":"Stalikas","year":"2020","journal-title":"J Clin Med"},{"key":"2026062608022910000_10.9.e038012.31","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu352"},{"key":"2026062608022910000_10.9.e038012.32","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.113.000817"},{"key":"2026062608022910000_10.9.e038012.33","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ahj.2019.08.002","article-title":"A multi-national trial of a direct oral anticoagulant in children with cardiac disease: design and rationale of the safety of apixaban on pediatric heart disease on the preventioN of embolism (saxophone) study","volume":"217","author":"Payne","year":"2019","journal-title":"Am Heart J"},{"key":"2026062608022910000_10.9.e038012.34","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ahj.2019.04.009","article-title":"Rivaroxaban, a direct factor Xa inhibitor, versus acetylsalicylic acid as thromboprophylaxis in children post-Fontan procedure: rationale and design of a prospective, randomized trial (the universe study)","volume":"213","author":"Pina","year":"2019","journal-title":"Am Heart J"},{"key":"2026062608022910000_10.9.e038012.35","unstructured":"U.S . Department of health and human services food and drug administration. Non-Inferiority Clinical Trials to Establish Effectiveness: Guidance for Industry, 2016."},{"key":"2026062608022910000_10.9.e038012.36","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw233"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2020-038012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:08:49Z","timestamp":1782486529000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2020-038012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9,22]]},"published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1136\/bmjopen-2020-038012"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2020-038012","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9]]}}}