{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:22:23Z","timestamp":1792686143927,"version":"4.5.0"},"reference-count":37,"publisher":"Georg Thieme Verlag KG","issue":"02","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82100273"],"award-info":[{"award-number":["82100273"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003453","name":"Guangdong Natural Science Foundation","doi-asserted-by":"crossref","award":["2023A1515012798"],"award-info":[{"award-number":["2023A1515012798"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>\n            Background\u2003The aim of the present meta-analysis was to evaluate the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with polypharmacy.<\/jats:p><jats:p>\n            Methods and Results\u2003Randomized controlled trials or observational studies reporting the data of NOACs versus VKAs among AF patients with polypharmacy were included. The search was performed in the PubMed and Embase databases up to November 2022. A total of 12 studies involving 767,544 AF patients were included. For the primary outcomes, the use of NOACs compared with VKAs was significantly associated with a reduced risk of stroke or systemic embolism in AF patients with moderate polypharmacy (hazard ratio [HR]: 0.77 [95% confidence interval [CI]: 0.69\u20130.86]) and severe polypharmacy (HR: 0.76 [95% CI: 0.69\u20130.82]), but there was no significant difference in major bleeding (moderate polypharmacy: HR: 0.87 [95% CI: 0.74\u20131.01]; severe polypharmacy: HR: 0.91 [95% CI: 0.79\u20131.06]) between the two groups. In secondary outcomes, there were no differences in the rates of ischemic stroke, all-cause death, and gastrointestinal bleeding between the NOAC- and VKA- users, but NOAC users had a reduced risk of any bleeding compared with VKA- users. Compared with VKAs, the risk of intracranial hemorrhage was reduced in NOAC- users with moderate polypharmacy but not severe polypharmacy.<\/jats:p><jats:p>\n            Conclusion\u2003In patients with AF and polypharmacy, NOACs showed advantages over VKAs in stroke or systemic embolism and any bleeding, and were comparable to VKAs for major bleeding, ischemic stroke, all-cause death, intracranial hemorrhage, and gastrointestinal bleeding.<\/jats:p>","DOI":"10.1055\/s-0043-1770724","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T23:03:05Z","timestamp":1688425385000},"page":"166-177","source":"Crossref","is-referenced-by-count":35,"title":["Effect of Oral Anticoagulants in Atrial Fibrillation Patients with Polypharmacy: A Meta-analysis"],"prefix":"10.1055","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-6327","authenticated-orcid":false,"given":"Yuxiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7566-1626","authenticated-orcid":false,"given":"Gregory Y. H.","family":"Lip","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom"},{"name":"Department of Clinical Medicine, Aalborg University, Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang of Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wengen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.arr.2018.10.006","article-title":"Overview of oral antithrombotic treatment in elderly patients with atrial fibrillation","volume":"49","author":"E T Kato","year":"2019","journal-title":"Ageing Res Rev"},{"issue":"10","key":"ref2","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1093\/europace\/euz141","article-title":"Prevalence of atrial fibrillation in the Italian elderly population and projections from 2020 to 2060 for Italy and the European Union: the FAI Project","volume":"21","author":"A Di Carlo","year":"2019","journal-title":"Europace"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12877-017-0621-2","article-title":"What is polypharmacy? A systematic review of definitions","volume":"17","author":"N Masnoon","year":"2017","journal-title":"BMC Geriatr"},{"issue":"12","key":"ref4","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1056\/NEJMoa0905561","article-title":"Dabigatran versus warfarin in patients with atrial fibrillation","volume":"361","author":"S J Connolly","year":"2009","journal-title":"N Engl J Med"},{"issue":"22","key":"ref5","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1056\/NEJMoa1310907","article-title":"Edoxaban versus warfarin in patients with atrial fibrillation","volume":"369","author":"R P Giugliano","year":"2013","journal-title":"N Engl J Med"},{"issue":"11","key":"ref6","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1056\/NEJMoa1107039","article-title":"Apixaban versus warfarin in patients with atrial fibrillation","volume":"365","author":"C B Granger","year":"2011","journal-title":"N Engl J Med"},{"issue":"10","key":"ref7","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1009638","article-title":"Rivaroxaban versus warfarin in nonvalvular atrial fibrillation","volume":"365","author":"M R Patel","year":"2011","journal-title":"N Engl J Med"},{"issue":"03","key":"ref8","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/jgs.15712","article-title":"Relevance of polypharmacy for clinical outcome in patients receiving vitamin K antagonists","volume":"67","author":"L Eggebrecht","year":"2019","journal-title":"J Am Geriatr Soc"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"i2868","DOI":"10.1136\/bmj.i2868","article-title":"Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial","volume":"353","author":"J Jaspers Focks","year":"2016","journal-title":"BMJ"},{"issue":"04","key":"ref10","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1161\/CIRCULATIONAHA.115.018544","article-title":"Polypharmacy and the efficacy and safety of rivaroxaban versus warfarin in the prevention of stroke in patients with nonvalvular atrial fibrillation","volume":"133","author":"J P Piccini","year":"2016","journal-title":"Circulation"},{"issue":"01","key":"ref11","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1055\/s-0041-1739411","article-title":"2021 Focused Update Consensus Guidelines of the Asia Pacific Heart Rhythm Society on Stroke Prevention in Atrial Fibrillation: executive summary","volume":"122","author":"T F Chao","year":"2022","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref12","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","article-title":"2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC","volume":"42","author":"G Hindricks","year":"2021","journal-title":"Eur Heart J"},{"issue":"03","key":"ref13","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1046\/j.1525-1497.1998.00053.x","article-title":"The interaction of patient perception of overmedication with drug compliance and side effects","volume":"13","author":"B G Fincke","year":"1998","journal-title":"J Gen Intern Med"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/jgs.15767","article-title":"American Geriatrics Society 2019 Updated AGS Beers Criteria\u00ae for potentially inappropriate medication use in older adults","volume":"67","author":"By the 2019 American Geriatrics Society Beers Criteria\u00ae Update Expert Panel","year":"2019","journal-title":"J Am Geriatr Soc"},{"issue":"05","key":"ref15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/ehjcvp\/pvaa117","article-title":"Effectiveness and safety of oral anticoagulants among non-valvular atrial fibrillation patients with polypharmacy","volume":"7","author":"G YH Lip","year":"2021","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"issue":"05","key":"ref16","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s10557-019-06907-8","article-title":"Impact of polypharmacy and P-glycoprotein- and CYP3A4-modulating drugs on safety and efficacy of oral anticoagulation therapy in patients with atrial fibrillation","volume":"33","author":"R E Harskamp","year":"2019","journal-title":"Cardiovasc Drugs Ther"},{"issue":"06","key":"ref17","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s10557-018-6825-7","article-title":"Predictors of major bleeding among working-age adults with atrial fibrillation: evaluating the effects of potential drug-drug interactions and switching from warfarin to non-vitamin K oral anticoagulants","volume":"32","author":"X Feng","year":"2018","journal-title":"Cardiovasc Drugs Ther"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.18433\/J30W4F","article-title":"Predictors of direct oral anticoagulants utilization for thromboembolism prevention in atrial fibrillation","volume":"20","author":"C Brais","year":"2017","journal-title":"J Pharm Pharm Sci"},{"issue":"08","key":"ref19","doi-asserted-by":"crossref","first-page":"e0238233","DOI":"10.1371\/journal.pone.0238233","article-title":"Predictive factors associated with bleeding in atrial fibrillation patients treated with anti-coagulant drugs using a large claims database","volume":"15","author":"K Momo","year":"2020","journal-title":"PLoS One"},{"issue":"12","key":"ref20","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1007\/s00228-017-2337-9","article-title":"Bleeding-related admissions in patients with atrial fibrillation receiving antithrombotic therapy: results from the Tasmanian Atrial Fibrillation (TAF) study","volume":"73","author":"E Admassie","year":"2017","journal-title":"Eur J Clin Pharmacol"},{"issue":"05","key":"ref21","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/jcpt.12999","article-title":"Factors related to inappropriate edoxaban use","volume":"44","author":"B M Jang","year":"2019","journal-title":"J Clin Pharm Ther"},{"issue":"02","key":"ref22","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1136\/ejhpharm-2017-001390","article-title":"Hospital admissions for bleeding events associated with treatment with apixaban, dabigatran and rivaroxaban","volume":"26","author":"J L Marco Garbayo","year":"2019","journal-title":"Eur J Hosp Pharm Sci Pract"},{"issue":"04","key":"ref23","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s40256-021-00520-7","article-title":"Effectiveness and safety of rivaroxaban versus warfarin among nonvalvular atrial fibrillation patients with obesity and polypharmacy","volume":"22","author":"M J Alberts","year":"2022","journal-title":"Am J Cardiovasc Drugs"},{"issue":"07","key":"ref24","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1007\/s12325-021-01746-2","article-title":"Comparative effectiveness and safety of rivaroxaban and warfarin among nonvalvular atrial fibrillation (NVAF) patients with obesity and polypharmacy in the United States (US)","volume":"38","author":"J S Berger","year":"2021","journal-title":"Adv Ther"},{"issue":"11","key":"ref25","doi-asserted-by":"crossref","first-page":"e015089","DOI":"10.1161\/JAHA.119.015089","article-title":"Polypharmacy, adverse outcomes, and treatment effectiveness in patients \u226575 with atrial fibrillation","volume":"9","author":"N Chen","year":"2020","journal-title":"J Am Heart Assoc"},{"issue":"02","key":"ref26","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/phar.2213","article-title":"Influence of polypharmacy on the effectiveness and safety of rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation","volume":"39","author":"B K Martinez","year":"2019","journal-title":"Pharmacotherapy"},{"issue":"07","key":"ref27","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1161\/STROKEAHA.120.029541","article-title":"Comparative effectiveness of rivaroxaban, apixaban, and warfarin in atrial fibrillation patients with polypharmacy","volume":"51","author":"A Mentias","year":"2020","journal-title":"Stroke"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.amjcard.2021.03.024","article-title":"Cardiovascular outcomes according to polypharmacy and drug adherence in patients with atrial fibrillation on long-term anticoagulation (from the RE-LY trial)","volume":"149","author":"D Millenaar","year":"2021","journal-title":"Am J Cardiol"},{"issue":"04","key":"ref29","doi-asserted-by":"crossref","first-page":"e417","DOI":"10.1055\/s-0040-1721499","article-title":"The number of concomitant drugs and the safety of direct oral anticoagulants in routine care patients with atrial fibrillation","volume":"4","author":"C J van den Dries","year":"2020","journal-title":"TH Open"},{"issue":"01","key":"ref30","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1253\/circj.CJ-22-0170","article-title":"Effect of polypharmacy on clinical outcomes in elderly patients with non-valvular atrial fibrillation\u3000- a sub-analysis of the ANAFIE registry","volume":"87","author":"T Yamashita","year":"2022","journal-title":"Circ J"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0140-6736(13)62343-0","article-title":"Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials","volume":"383","author":"C T Ruff","year":"2014","journal-title":"Lancet"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2018.10.005","article-title":"Non-vitamin K oral anticoagulants (NOAC) and the risk of myocardial infarction: differences between factor IIa and factor Xa inhibition?","volume":"195","author":"A Polzin","year":"2019","journal-title":"Pharmacol Ther"},{"issue":"11","key":"ref33","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1177\/1060028013504741","article-title":"Pharmacokinetic and pharmacodynamic drug interactions with new oral anticoagulants: what do they mean for patients with atrial fibrillation?","volume":"47","author":"T Hellwig","year":"2013","journal-title":"Ann Pharmacother"},{"issue":"16","key":"ref34","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1093\/eurheartj\/ehy136","article-title":"The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation","volume":"39","author":"J Steffel","year":"2018","journal-title":"Eur Heart J"},{"issue":"08","key":"ref35","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/S0149-2918(01)80109-0","article-title":"A systematic review of the associations between dose regimens and medication compliance","volume":"23","author":"A J Claxton","year":"2001","journal-title":"Clin Ther"},{"issue":"02","key":"ref36","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1161\/CIRCOUTCOMES.115.002366","article-title":"Reimagining anticoagulation clinics in the era of direct oral anticoagulants","volume":"9","author":"G D Barnes","year":"2016","journal-title":"Circ Cardiovasc Qual Outcomes"},{"issue":"11","key":"ref37","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1093\/europace\/euab091","article-title":"Persistence and adherence to non-vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation across five Western European countries","volume":"23","author":"J J Komen","year":"2021","journal-title":"Europace"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-1770724.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T23:32:17Z","timestamp":1738366337000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-1770724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,3]]},"references-count":37,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2025,1,31]]},"published-print":{"date-parts":[[2025,2]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-1770724","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,3]]}}}