{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:41:49Z","timestamp":1792291309392,"version":"4.4.0"},"reference-count":32,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:p>\n            Background\u2003Phase II randomized controlled trials (RCTs) on factor(F)XI inhibitors have shown promising results but they were burdened by low statistical power for clinical outcomes.<\/jats:p><jats:p>\n            Methods\u2003We performed a systematic review and meta-analysis of RCT comparing FXI inhibitors versus other anticoagulants (enoxaparin or direct oral anticoagulants, DOACs) or versus placebo on top of antiplatelet therapy.<\/jats:p><jats:p>\n            Results\u2003Eight RCTs testing FXI inhibitors (ISIS 416858, osocimab, abelacimab, milvexian, asundexian) and enrolling 9,216 patients were included. Compared with enoxaparin, FXI inhibitors were associated with reduced any-bleeding (risk ratio [RR]: 0.49, 95% confidence interval [CI]: 0.31\u20130.77), no difference in major bleeding (RR: 0.96, 95% CI: 0.41\u20132.28), and reduced trial-defined efficacy endpoint (RR: 0.62, 95% CI: 0.49\u20130.79), the latter driven by the high-dose regimens. Compared with DOACs, FXI inhibitors were associated with a trend toward reduced any-bleeding (RR: 0.66, 95% CI: 0.31\u20131.38) and no difference in major bleeding (RR: 1.03, 95% CI: 0.22\u20134.78) or in trial-defined efficacy endpoint (RR: 1.23, 95% CI: 0.88\u20131.70). Compared with placebo, FXI inhibitors were associated with increased any-bleeding (RR: 1.25, 95% CI: 1.08\u20131.43) and a trend toward increased major bleeding (RR: 1.21, 95% CI: 0.75\u20131.93), both driven by high-dose regimens, with no difference in trial-defined efficacy endpoint (RR: 1.02, 95% CI: 0.92\u20131.13).<\/jats:p><jats:p>\n            Conclusion\u2003Results of this meta-analysis on FXI inhibitors suggest increased safety and efficacy compared with enoxaparin and modest increased safety compared with DOACs. The use of FXI inhibitors in adjunct to antiplatelet therapy versus placebo appears to be associated with a dose-dependent increase in bleeding without any difference in efficacy.<\/jats:p><jats:p>\n            Study registration\u2003This study is registered in PROSPERO (CRD42022367706).<\/jats:p>","DOI":"10.1055\/a-2043-0346","type":"journal-article","created":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T23:34:16Z","timestamp":1677368056000},"page":"576-584","source":"Crossref","is-referenced-by-count":56,"title":["Factor XI Inhibitors in Early Clinical Trials: A Meta-analysis"],"prefix":"10.1055","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3909-182X","authenticated-orcid":false,"given":"Mattia","family":"Galli","sequence":"additional","affiliation":[{"name":"Catholic University of the Sacred Heart, Rome, Italy"},{"name":"Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Laborante","sequence":"additional","affiliation":[{"name":"Catholic University of the Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Ortega-Paz","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Franchi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Rollini","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"D'Amario","sequence":"additional","affiliation":[{"name":"Dipartimento Universitario di Medicina Traslazionale, Universit\u00e0 Piemonte Orientale, Azienda Ospedaliero-Universitaria Maggiore della Carit\u00e0 di Novara, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5156-7723","authenticated-orcid":false,"given":"Davide","family":"Capodanno","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Azienda Ospedaliero Universitaria Policlinico \u201cG. Rodolico-San Marco,\u201d University of Catania, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tremoli","sequence":"additional","affiliation":[{"name":"Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Micheal","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Mehran","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8451-2131","authenticated-orcid":false,"given":"Dominick J.","family":"Angiolillo","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,3,24]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"e44S","DOI":"10.1378\/chest.11-2292","article-title":"Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines","volume":"141","author":"W Ageno","year":"2012","journal-title":"Chest"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/eurheartj\/ehz405","article-title":"2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS)","volume":"41","author":"S V Konstantinides","year":"2020","journal-title":"Eur Heart J"},{"issue":"05","key":"ref3","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":"11","key":"ref4","first-page":"804","article-title":"Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial","volume":"38","author":"M Valgimigli","year":"2017","journal-title":"Eur Heart J"},{"issue":"08","key":"ref5","doi-asserted-by":"crossref","first-page":"286","DOI":"10.31083\/j.rcm2308286","article-title":"Bleeding complications in patients undergoing percutaneous coronary intervention","volume":"23","author":"M Galli","year":"2022","journal-title":"Rev Cardiovasc Med"},{"issue":"06","key":"ref6","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.jacc.2021.06.010","article-title":"Factor XI inhibition to uncouple thrombosis from hemostasis: JACC Review Topic of the Week","volume":"78","author":"C Hsu","year":"2021","journal-title":"J Am Coll Cardiol"},{"issue":"04","key":"ref7","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1093\/eurheartj\/ehac464","article-title":"Factor XI inhibitors: cardiovascular perspectives","volume":"44","author":"R De Caterina","year":"2023","journal-title":"Eur Heart J"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement","volume":"4","author":"D Moher","year":"2015","journal-title":"Syst Rev"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"J PT Higgins","year":"2011","journal-title":"BMJ"},{"issue":"23","key":"ref10","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1161\/CIRCULATIONAHA.110.009449","article-title":"Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium","volume":"123","author":"R Mehran","year":"2011","journal-title":"Circulation"},{"issue":"02","key":"ref11","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/jrsm.12","article-title":"A basic introduction to fixed-effect and random-effects models for meta-analysis","volume":"1","author":"M Borenstein","year":"2010","journal-title":"Res Synth Methods"},{"issue":"01","key":"ref12","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/jrsm.1230","article-title":"Basics of meta-analysis: I2 is not an absolute measure of heterogeneity","volume":"8","author":"M Borenstein","year":"2017","journal-title":"Res Synth Methods"},{"issue":"07","key":"ref13","doi-asserted-by":"crossref","first-page":"e99682","DOI":"10.1371\/journal.pone.0099682","article-title":"Evaluating the quality of evidence from a network meta-analysis","volume":"9","author":"G Salanti","year":"2014","journal-title":"PLoS One"},{"issue":"17","key":"ref14","doi-asserted-by":"crossref","first-page":"e1371","DOI":"10.4244\/EIJ-D-21-00904","article-title":"Antiplatelet therapy after percutaneous coronary intervention","volume":"17","author":"D J Angiolillo","year":"2022","journal-title":"EuroIntervention"},{"key":"ref15","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"},{"issue":"02","key":"ref16","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1093\/ehjcvp\/pvv002","article-title":"New oral anticoagulants: a practical guide for physicians","volume":"1","author":"R Hinojar","year":"2015","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"issue":"01","key":"ref17","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1093\/ehjcvp\/pvw031","article-title":"A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants","volume":"3","author":"S Halvorsen","year":"2017","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"issue":"37","key":"ref18","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1093\/eurheartj\/ehac294","article-title":"Great debate: triple antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting should be limited to 1 week","volume":"43","author":"R De Caterina","year":"2022","journal-title":"Eur Heart J"},{"issue":"04","key":"ref19","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/s41569-019-0314-y","article-title":"Dual-pathway inhibition for secondary and tertiary antithrombotic prevention in cardiovascular disease","volume":"17","author":"D Capodanno","year":"2020","journal-title":"Nat Rev Cardiol"},{"issue":"01","key":"ref20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/17512433.2023.2154651","article-title":"Dual pathway inhibition in patients with atherosclerotic disease: pharmacodynamic considerations and clinical implications","volume":"16","author":"M Galli","year":"2023","journal-title":"Expert Rev Clin Pharmacol"},{"issue":"05","key":"ref21","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1093\/ehjcvp\/pvab043","article-title":"Efficacy and safety of dual-pathway inhibition in patients with cardiovascular disease: a meta-analysis of 49 802 patients from 7 randomized trials","volume":"8","author":"M Galli","year":"2022","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"issue":"09","key":"ref22","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1056\/NEJMra0801082","article-title":"Mechanisms of thrombus formation","volume":"359","author":"B Furie","year":"2008","journal-title":"N Engl J Med"},{"issue":"07","key":"ref23","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1056\/NEJMoa2105872","article-title":"Abelacimab for prevention of venous thromboembolism","volume":"385","author":"P Verhamme","year":"2021","journal-title":"N Engl J Med"},{"issue":"03","key":"ref24","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1056\/NEJMoa1405760","article-title":"Factor XI antisense oligonucleotide for prevention of venous thrombosis","volume":"372","author":"H R B\u00fcller","year":"2015","journal-title":"N Engl J Med"},{"issue":"02","key":"ref25","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1001\/jama.2019.20687","article-title":"Effect of osocimab in preventing venous thromboembolism among patients undergoing knee arthroplasty: the FOXTROT randomized clinical trial","volume":"323","author":"J I Weitz","year":"2020","journal-title":"JAMA"},{"issue":"23","key":"ref26","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1056\/NEJMoa2113194","article-title":"Milvexian for the prevention of venous thromboembolism","volume":"385","author":"J I Weitz","year":"2021","journal-title":"N Engl J Med"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"903029","DOI":"10.3389\/fcvm.2022.903029","article-title":"Factor XI inhibitors for prevention and treatment of venous thromboembolism: a review on the rationale and update on current evidence","volume":"9","author":"S Nopp","year":"2022","journal-title":"Front Cardiovasc Med"},{"issue":"12","key":"ref28","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1111\/jth.15890","article-title":"Achieving higher efficacy without compromising safety with factor XI inhibitors versus low molecular weight heparin for the prevention of venous thromboembolism in major orthopedic surgery-systematic review and meta-analysis","volume":"20","author":"J Presume","year":"2022","journal-title":"J Thromb Haemost"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/S0140-6736(22)00456-1","article-title":"Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study","volume":"399","author":"J P Piccini","year":"2022","journal-title":"Lancet"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/S0140-6736(22)01588-4","article-title":"Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial","volume":"400","author":"A Shoamanesh","year":"2022","journal-title":"Lancet"},{"issue":"16","key":"ref31","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1161\/CIRCULATIONAHA.122.061612","article-title":"A multicenter, phase 2, randomized, placebo-controlled, double-blind, parallel-group, dose-finding trial of the oral factor XIa inhibitor asundexian to prevent adverse cardiovascular outcomes after acute myocardial infarction","volume":"146","author":"S V Rao","year":"2022","journal-title":"Circulation"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(09)60738-8","article-title":"Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial","volume":"374","author":"J L Mega","year":"2009","journal-title":"Lancet"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2043-0346.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T23:41:53Z","timestamp":1684885313000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2043-0346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,25]]},"references-count":32,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2023,5,23]]},"published-print":{"date-parts":[[2023,6]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2043-0346","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,2,25]]},"published":{"date-parts":[[2023,2,25]]}}}