{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:28:32Z","timestamp":1789687712712,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial fibrillation. We performed a systematic review and meta\u2010analysis assessing the risk of ischaemic stroke, thromboembolism (TE) and intracranial haemorrhage (ICH) associated with the use of DOACs and VKAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age and sex were performed. A random\u2010effects model was used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke (HR: 0.82, 95% CI: 0.68\u20130.99) compared to dabigatran. Rivaroxaban was associated with lower risk of stroke (HR: 0.90, 95% CI: 0.83\u20130.98) compared to VKA. Dabigatran (HR: 0.85, 95% CI: 0.80\u20130.91), rivaroxaban (HR: 0.83, 95% CI: 0.77\u20130.89) and apixaban (HR: 0.75, 95% CI: 0.65\u20130.86) were associated with lower risk for TE\/stroke compared to VKA. Apixaban (HR: 1.32, 95% CI: 1.03\u20131.68) and rivaroxaban (HR: 1.58, 95% CI: 1.31\u20131.89) were associated with higher risk of ICH compared to dabigatran. Dabigatran (HR: 0.48, 95% CI: 0.44\u20130.52), apixaban (HR: 0.60, 95% CI: 0.49\u20130.73) and rivaroxaban (HR: 0.73, 95% CI: 0.65\u20130.81) were associated with lower risk of ICH compared to VKA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrated significant differences in the risk of ischaemic stroke, TE\/stroke and ICH associated with individual DOACs compared to both other DOACs and VKA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15464","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T23:45:00Z","timestamp":1658274300000},"page":"4663-4675","source":"Crossref","is-referenced-by-count":15,"title":["Effectiveness and safety of intracranial events associated with the use of direct oral anticoagulants for atrial fibrillation: A systematic review and meta\u2010analysis of 92 studies"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6660-6916","authenticated-orcid":false,"given":"Paraschos","family":"Archontakis\u2010Barakakis","sequence":"first","affiliation":[{"name":"Northeast Internal Medicine Associates  LaGrange IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine Albert Einstein College of Medicine\/Jacobi Medical Center  Bronx NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Kalaitzoglou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery King's College Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lazaros","family":"Tzelves","sequence":"additional","affiliation":[{"name":"2nd Department of Urology National and Kapodistrian University of Athens, Sismanogleion Hospital  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolos","family":"Manolopoulos","sequence":"additional","affiliation":[{"name":"Department of Neurology General Hospital of Elefsina Thriasio  Attiki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanos","family":"Giannopoulos","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Surgery Stony Brook University Hospital  Stony Brook NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigorios","family":"Giamouzis","sequence":"additional","affiliation":[{"name":"Department of Cardiology University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly  Larisa Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Giannakoulas","sequence":"additional","affiliation":[{"name":"Division of Cardiology, AHEPA University Hospital Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolos","family":"Batsidis","sequence":"additional","affiliation":[{"name":"Department of Mathematics University of Ioannina  Ioannina Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas","family":"Palaiodimos","sequence":"additional","affiliation":[{"name":"Department of Medicine Albert Einstein College of Medicine\/Jacobi Medical Center  Bronx NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Ntaios","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Thessaly  Larissa Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y. H.","family":"Lip","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart &amp; Chest Hospital  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damianos G.","family":"Kokkinidis","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine Yale University School of Medicine, Yale New Haven Hospital  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2013.05.063"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(16)31257\u20100"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.002329"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjqcco\/qcaa093"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003\u20104819\u2010139\u201012\u2010200312160\u201000011"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa612"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.153"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100039\u20101693516"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1515-9630"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2015.05.044"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905561"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009638"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107039"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310907"},{"issue":"1","key":"e_1_2_10_16_1","first-page":"S21","article-title":"THE CONCISE GUIDE TO PHARMACOLOGY 2019\/20: G protein\u2010coupled receptors","volume":"176","author":"Alexander SPH","year":"2019","journal-title":"Br J Pharmacol"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000100"},{"issue":"4","key":"e_1_2_10_18_1","first-page":"175","article-title":"ROBINS\u20101: A tool for asssessing risk of bias in non\u2010randomised studies of interventions","volume":"40","author":"Hinneburg I","year":"2017","journal-title":"Med Monatsschr Pharm"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.017549"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.018395"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v13.i4.82"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15464","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.15464","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15464","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T08:55:20Z","timestamp":1692608120000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.15464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,15]]},"references-count":20,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1111\/bcp.15464"],"URL":"https:\/\/doi.org\/10.1111\/bcp.15464","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,15]]}}}