{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:54:57Z","timestamp":1773251697941,"version":"3.50.1"},"reference-count":44,"publisher":"BMJ","issue":"6","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2014,5,9]]},"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard adjusted dose (target international normalised ratio 2.0\u20133.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial fibrillation and among subpopulations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Systematic review and network meta-analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Data sources<\/jats:title>\n                  <jats:p>A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and the grey literature including the websites of regulatory agencies and health technology assessment organisations for trials published in English from 1988 to January 2014.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Eligibility criteria for selecting studies<\/jats:title>\n                  <jats:p>Randomised controlled trials were selected for inclusion if they were published in English, included at least one antithrombotic treatment and involved patients with non-valvular atrial fibrillation eligible to receive anticoagulant therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For stroke or systemic embolism, dabigatran 150\u2005mg and apixaban twice daily were associated with reductions relative to standard adjusted dose VKA, whereas low-dose ASA and the combination of clopidogrel plus low-dose ASA were associated with increases. Absolute risk reductions ranged from 6 fewer events per 1000 patients treated for dabigatran 150\u2005mg twice daily to 15 more events for clopidogrel plus ASA. For major bleeding, edoxaban 30\u2005mg daily, apixaban, edoxaban 60\u2005mg daily and dabigatran 110\u2005mg twice daily were associated with reductions compared to standard adjusted dose VKA. Absolute risk reductions with these agents ranged from 18 fewer per 1000 patients treated each year for edoxaban 30\u2005mg daily to 24 more for medium dose ASA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Compared with standard adjusted dose VKA, new oral anticoagulants were associated with modest reductions in the absolute risk of stroke and major bleeding. People on antiplatelet drugs experienced more strokes compared with anticoagulant drugs without any reduction in bleeding risk. To fully elucidate the comparative benefits and harms of antithrombotic agents across the various subpopulations, rigorously conducted comparative studies or network meta-regression analyses of patient-level data are required.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Systematic review registration number<\/jats:title>\n                  <jats:p>PROSPERO registry\u2014CRD42012002721.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2013-004301","type":"journal-article","created":{"date-parts":[[2014,6,2]],"date-time":"2014-06-02T23:52:52Z","timestamp":1401753172000},"page":"e004301","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":92,"title":["Systematic review and network meta-analysis comparing antithrombotic agents for the prevention of stroke and major bleeding in patients with atrial fibrillation"],"prefix":"10.1136","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3613-760X","authenticated-orcid":false,"given":"Chris","family":"Cameron","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada"},{"name":"University of Ottawa Heart Institute, Ottawa, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doug","family":"Coyle","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trevor","family":"Richter","sequence":"additional","affiliation":[{"name":"Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon","family":"Kelly","sequence":"additional","affiliation":[{"name":"University of Ottawa Heart Institute, Ottawa, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kasandra","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Steiner","sequence":"additional","affiliation":[{"name":"Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Carrier","sequence":"additional","affiliation":[{"name":"Thrombosis Program, Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Coyle","sequence":"additional","affiliation":[{"name":"Applied Health Economics Research Unit, Ottawa, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie","family":"Bai","sequence":"additional","affiliation":[{"name":"Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Moulton","sequence":"additional","affiliation":[{"name":"Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tammy","family":"Clifford","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada"},{"name":"Canadian Agency for Drugs and Technologies in Health, Ottawa, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada"},{"name":"University of Ottawa Heart Institute, Ottawa, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2014,6,2]]},"reference":[{"key":"2025101814195842000_4.6.e004301.1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs446"},{"key":"2025101814195842000_4.6.e004301.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2012.01.021"},{"key":"2025101814195842000_4.6.e004301.3","unstructured":"Antithrombotic agents for the prevention of stroke and systemic embolism in patients with atrial fibrillation. 2013. http:\/\/www.cadth.ca\/media\/pdf\/TR0003_AntithromboticAgents-AF_ScienceReport-e.pdf"},{"key":"2025101814195842000_4.6.e004301.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01204.x"},{"key":"2025101814195842000_4.6.e004301.5","unstructured":"NHS Quality Improvement Scotland (NHS QIS). SIGN 50. A guideline developer's handbook. 2008. http:\/\/www.sign.ac.uk\/pdf\/sign50.pdf"},{"key":"2025101814195842000_4.6.e004301.6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000097"},{"key":"2025101814195842000_4.6.e004301.7","doi-asserted-by":"crossref","unstructured":"Dias S, Sutton AJ, Ades a E, et al. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Making 2013;33:607\u201317.","DOI":"10.1177\/0272989X12458724"},{"key":"2025101814195842000_4.6.e004301.8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905561"},{"key":"2025101814195842000_4.6.e004301.9","unstructured":"Ingelheim B . Advisory committee briefing document: dabigatran etexilate [Internet]. 2010:1\u2013168. http:\/\/www.fda.gov\/downloads\/advisorycommittees\/committeesmeetingmaterials\/drugs\/cardiovas"},{"key":"2025101814195842000_4.6.e004301.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60046-5"},{"key":"2025101814195842000_4.6.e004301.11","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dys041"},{"key":"2025101814195842000_4.6.e004301.12","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/1467-9868.00353","article-title":"Bayesian measures of model complexity and fit","volume":"64","author":"Spiegelhalter","year":"2002","journal-title":"J R Stat Soc Ser B (Statistical Methodol)"},{"key":"2025101814195842000_4.6.e004301.13","unstructured":"Spiegelhalter D Thomas A Best N . WinBUGS user manual. MRC Biostat Unit, 2004:2."},{"key":"2025101814195842000_4.6.e004301.14","unstructured":"meta: Meta-Analysis with R. http:\/\/cran.r-project.org\/web\/packages\/meta\/index.html ."},{"key":"2025101814195842000_4.6.e004301.15","doi-asserted-by":"crossref","unstructured":"Dias S, Welton NJ, Sutton AJ, et al. Evidence synthesis for decision making 4: inconsistency in networks of evidence based on randomized controlled trials. Med Decis Making 2013;33:641\u201356.","DOI":"10.1177\/0272989X12455847"},{"key":"2025101814195842000_4.6.e004301.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2008.10.001"},{"key":"2025101814195842000_4.6.e004301.17","doi-asserted-by":"crossref","unstructured":"Wells G Coyle D Cameron C . Safety, effectiveness, and cost effectiveness of new oral anticoagulants compared with warfarin in preventing stroke and other cardiovascular events in patients with atrial fibrillation. 2012. http:\/\/www.cadth.ca\/media\/pdf\/NOAC_Therapeutic_Review_final_report.pdf","DOI":"10.1016\/j.jval.2013.01.009"},{"key":"2025101814195842000_4.6.e004301.18","unstructured":"Johnson & Johnson Pharmaceutical Research & Development. Rivaroxaban for the prevention of stroke and non-central nervous system (CNS) systemic embolism in patients with atrial fibrillation. 2011;7939:222."},{"key":"2025101814195842000_4.6.e004301.19","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.jclinepi.2013.05.006","article-title":"US Food and Drug Administration documents can provide unpublished evidence relevant to systematic reviews","volume":"66","author":"McDonagh","year":"2013","journal-title":"J Clin Epidemiol"},{"key":"2025101814195842000_4.6.e004301.20","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310907"},{"key":"2025101814195842000_4.6.e004301.21","unstructured":"Granger C Alexander J . Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011:981\u201392."},{"key":"2025101814195842000_4.6.e004301.22","doi-asserted-by":"crossref","unstructured":"Patel M Mahaffey K Garg J . Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011:883\u201391.","DOI":"10.1056\/NEJMoa1009638"},{"key":"2025101814195842000_4.6.e004301.23","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68845-4"},{"key":"2025101814195842000_4.6.e004301.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2007.06.034"},{"key":"2025101814195842000_4.6.e004301.25","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afl129"},{"key":"2025101814195842000_4.6.e004301.26","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1160\/TH10-07-0451","article-title":"Safety of edoxaban, an oral factor Xa inhibitor, in Asian patients with non-valvular atrial fibrillation","volume":"105","author":"Chung","year":"2011","journal-title":"Thromb Haemost"},{"key":"2025101814195842000_4.6.e004301.27","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-11-1140"},{"key":"2025101814195842000_4.6.e004301.28","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1007432"},{"key":"2025101814195842000_4.6.e004301.29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0901301"},{"key":"2025101814195842000_4.6.e004301.30","doi-asserted-by":"crossref","unstructured":"Healey JS, Hart RG, Pogue J, et al. Risks and benefits of oral anticoagulation compared with clopidogrel plus aspirin in patients with atrial fibrillation according to stroke risk: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE-W). Stroke 2008;39:1482\u20136.","DOI":"10.1161\/STROKEAHA.107.500199"},{"key":"2025101814195842000_4.6.e004301.31","doi-asserted-by":"crossref","first-page":"62","DOI":"10.5482\/HAMO-12-11-0021","article-title":"Clinical trials with new oral anticoagulants. Additive value of indirect comparisons also named network meta-analyses","volume":"33","author":"Harenberg","year":"2013","journal-title":"Hamostaseologie"},{"key":"2025101814195842000_4.6.e004301.32","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2013-304347"},{"key":"2025101814195842000_4.6.e004301.33","first-page":"1","article-title":"Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fi brillation: a meta-analysis of randomised trials","volume":"6736","author":"Ruff","year":"2013","journal-title":"Lancet"},{"key":"2025101814195842000_4.6.e004301.34","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.clinthera.2013.05.011","article-title":"Mixed treatment comparison meta-analysis of aspirin, warfarin, and new anticoagulants for stroke prevention in patients with nonvalvular atrial fibrillation","volume":"35","author":"Assiri","year":"2013","journal-title":"Clin Ther"},{"key":"2025101814195842000_4.6.e004301.35","doi-asserted-by":"crossref","unstructured":"Slot K Berge E . Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation. Stroke 2013. http:\/\/stroke.ahajournals.org\/content\/44\/12\/e165.short","DOI":"10.1161\/STROKEAHA.113.003453"},{"key":"2025101814195842000_4.6.e004301.36","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-148-7-200804010-00011"},{"key":"2025101814195842000_4.6.e004301.37","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.1021197"},{"key":"2025101814195842000_4.6.e004301.38","doi-asserted-by":"publisher","DOI":"10.1046\/j.1524-4733.2002.55150.x"},{"key":"2025101814195842000_4.6.e004301.39","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-4733.2009.00600.x"},{"key":"2025101814195842000_4.6.e004301.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2011.12.010"},{"key":"2025101814195842000_4.6.e004301.41","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1048"},{"key":"2025101814195842000_4.6.e004301.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.03.016"},{"key":"2025101814195842000_4.6.e004301.43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-4733.2010.00725.x"},{"key":"2025101814195842000_4.6.e004301.44","unstructured":"Boyd C Singh S Varadhan R . Methods research report methods for benefit and harm assessment in systematic reviews . 2012:52. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK115750\/"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2013-004301","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T21:20:07Z","timestamp":1760822407000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2013-004301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2014,6,2]]},"published-print":{"date-parts":[[2014,5]]}},"alternative-id":["10.1136\/bmjopen-2013-004301"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2013-004301","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5]]}}}