{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T05:43:58Z","timestamp":1783748638595,"version":"3.55.0"},"reference-count":38,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2024,7,2]]},"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Women with atrial fibrillation (AF) are under-represented in randomised controlled trials (RCTs) of direct oral anticoagulants (DOACs). This systematic review and meta-analysis of RCTs and observational studies examined sex-specific outcomes of DOACs in AF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>PubMed, Embase, Web of Science and Cochrane Library were searched from January 2008 to November 2022. Sex-specific comparative outcomes of stroke\/systemic embolism (SE), major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) between oral anticoagulants were pooled using random effects models. P values for interaction were calculated to examine differences in results between sexes. RCTs and observational studies were meta-analysed separately.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>5 RCTs and 33 observational studies were included, totalling 1 085 931\u2009women and 1 387 123 men. Meta-analyses showed that for both sexes, DOAC versus warfarin was generally associated with lower risk of stroke\/SE, major bleeding and ICH; in DOAC\u2013DOAC comparisons, rivaroxaban versus dabigatran had higher GIB risk. The only sex-specific difference observed was that when compared with warfarin, women had higher GIB risk with rivaroxaban (women: pooled risk ratio (pRR)=1.34, 95% CI=1.18 to 1.51; men: pRR=0.97, 95% CI=0.85 to 1.10; p value for interaction (p for interaction)&lt;0.001) and possibly dabigatran (women: pRR=1.25, 95% CI=0.92 to 1.70; men: pRR=0.83, 95% CI=0.72 to 0.97; p-for-interaction=0.02). The sex difference in GIB remained for rivaroxaban when a Bonferroni-corrected significance level was used (\u03b1=0.003). No sex-specific GIB data for apixaban and edoxaban was available for the meta-analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>For both sexes, DOACs generally demonstrated favourable effectiveness and safety over warfarin. However, observational data suggested that women may have higher GIB risk with rivaroxaban and possibly dabigatran than warfarin. Further studies are warranted to verify our findings and elucidate sex-specific GIB risk with apixaban and edoxaban, of which the data is currently lacking.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PROSPERO registration number<\/jats:title>\n                  <jats:p>CRD42022325027.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/openhrt-2024-002792","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:10:19Z","timestamp":1721175019000},"page":"e002792","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Sex-specific comparative outcomes between oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5904-1897","authenticated-orcid":false,"given":"Jan D","family":"Chobanov","sequence":"first","affiliation":[{"name":"Research Department of Practice and Policy, UCL School of Pharmacy, London, UK"},{"name":"Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Non-Communicable Disease Epidemiology, Faculty of Epidemiology & Population Health, London School of Hygiene and Tropical Medicines, London, UK"},{"name":"School of Pharmacy, Institute of Clinical Sciences, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK"},{"name":"Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth K C","family":"Man","sequence":"additional","affiliation":[{"name":"Research Department of Practice and Policy, UCL School of Pharmacy, London, UK"},{"name":"Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, UK"},{"name":"Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, Hong Kong"},{"name":"Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edil","family":"Dayib","sequence":"additional","affiliation":[{"name":"Research Department of Practice and Policy, UCL School of Pharmacy, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y H","family":"Lip","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK"},{"name":"Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aroon D","family":"Hingorani","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, University College London and University College London British Heart Foundation Research Accelerator, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai K","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C K","family":"Wong","sequence":"additional","affiliation":[{"name":"Research Department of Practice and Policy, UCL School of Pharmacy, London, UK"},{"name":"Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS 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