{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:57:18Z","timestamp":1793145438111,"version":"4.5.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>The incidence and mortality of thrombotic diseases in the aged population are increasing year by year, which seriously affect the quality of life of the elderly. At present, antithrombotic drugs used in clinical practice have good efficacy, but they caused different degrees of age-dependent bleeding risk. Therefore, there is an urgent need to develop effective antithrombotic drugs with less risk of bleeding. Recent studies have shown that factor \u216a inhibitors can effectively reduce the incidence of thromboembolic events without increasing the risk of bleeding. Therefore, factor \u216a inhibitors are expected to be safe and effective new anticoagulants, providing a new sight for the prevention and treatment of thrombotic diseases. This paper reviews the biological functions of factor \u216a, the types and characteristics of factor \u216a inhibitors and the related research progress of factor \u216a inhibitors.<\/jats:p>","DOI":"10.3389\/fcvm.2025.1498826","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:43:24Z","timestamp":1748583804000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Factor XI inhibitors are the novel promising anticoagulants in the treatment of age related thrombotic disease"],"prefix":"10.3389","volume":"12","author":[{"given":"Dandan","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianchun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","article-title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010","volume":"380","author":"Lozano","year":"2012","journal-title":"Lancet"},{"key":"B2","first-page":"311","article-title":"Prevention and treatment of thrombotic diseases in the elderly: according to the clinical guidance of \u201cChinese guidelines for the prevention and treatment of thrombotic diseases (2018)\u201d","volume":"22","author":"Zhi","year":"2019","journal-title":"Chin J Clin Healthcare"},{"key":"B3","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1161\/01.STR.0000196989.09900.f8","article-title":"Intracerebral hemorrhage associated with oral anticoagulant therapy: current practices and unresolved questions","volume":"37","author":"Steiner","year":"2006","journal-title":"Stroke"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1253\/circj.CJ-14-0720","article-title":"Impact of non-vitamin k antagonist oral anticoagulants on intracranial bleeding in Asian patients with non-valvular atrial fibrillation","volume":"78","author":"Yasaka","year":"2014","journal-title":"Circ J"},{"key":"B5","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1159\/000437150","article-title":"Epidemiology of intracranial haemorrhages associated with vitamin K antagonist oral anticoagulants in Spain: TAC registry","volume":"4","author":"Zapata-Wainberg","year":"2015","journal-title":"Interv Neurol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1160\/TH16-03-0203","article-title":"Dabigatran in real-world atrial fibrillation. Meta-analysis of observational comparison studies with vitamin K antagonists","volume":"116","author":"Carmo","year":"2016","journal-title":"Thromb Haemost"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1160\/TH17-01-0068","article-title":"Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in \u201creal-world\u201d clinical practice. A propensity-matched analysis of 76,940 patients","volume":"117","author":"Li","year":"2017","journal-title":"Thromb Haemost"},{"key":"B8","first-page":"173","article-title":"Efficacy of different anticoagulant drugs in elderly patients with non-valvular atrial fibrillation","volume":"31","author":"Na","year":"2021","journal-title":"Clin Med Pract"},{"key":"B9","first-page":"719","article-title":"Effect of three kinds of anticoagulant drugs on atrial fibrillation after radiofrequency catheter ablation: a network meta-analysis","volume":"48","author":"Yanhong","year":"2019","journal-title":"J Huazhong Univ Sci Technol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1002\/clc.23690","article-title":"Effects of rivaroxaban and warfarin on the risk of gastrointestinal bleeding and intracranial hemorrhage in patients with atrial fibrillation: systematic review and meta-analysis","volume":"44","author":"Jiang","year":"2021","journal-title":"Clin Cardiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"CD006650","DOI":"10.1002\/14651858.CD006650.pub5","article-title":"Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer","volume":"6","author":"Kahale","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1055\/s-0040-1712098","article-title":"Direct oral anticoagulants for the treatment of acute venous thromboembolism associated with cancer: a systematic review and meta-analysis","volume":"120","author":"Giustozzi","year":"2020","journal-title":"Thromb Haemost"},{"key":"B13","doi-asserted-by":"publisher","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":"Ruff","year":"2014","journal-title":"Lancet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1016\/S0140-6736(22)00563-3","article-title":"Making anticoagulation safer","volume":"399","author":"Gailani","year":"2022","journal-title":"Lancet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1055\/a-1384-3715","article-title":"Factor XI as a target for new anticoagulants","volume":"41","author":"Fredenburgh","year":"2021","journal-title":"Hamostaseologie"},{"key":"B16","doi-asserted-by":"publisher","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":"Hsu","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1182\/blood-2016-09-742262","article-title":"Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events","volume":"129","author":"Preis","year":"2017","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1161\/ATVBAHA.117.309846","article-title":"Tissue factor: an essential mediator of hemostasis and trigger of thrombosis","volume":"38","author":"Grover","year":"2018","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1161\/ATVBAHA.107.141911","article-title":"Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis","volume":"27","author":"Mackman","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.blre.2018.04.001","article-title":"Plasma contact factors as therapeutic targets","volume":"32","author":"Tillman","year":"2018","journal-title":"Blood Rev"},{"key":"B21","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1161\/ATVBAHA.118.312130","article-title":"Intrinsic pathway of coagulation and thrombosis","volume":"39","author":"Grover","year":"2019","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"7425","DOI":"10.1021\/acs.jmedchem.8b00173","article-title":"Factor XIa inhibitors as new anticoagulants","volume":"61","author":"Quan","year":"2018","journal-title":"J Med Chem"},{"key":"B23","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1097\/01.mbc.0000224843.33216.5f","article-title":"Factor XI enhances fibrin generation and inhibits fibrinolysis in a coagulation model initiated by surface-coated tissue factor","volume":"17","author":"von Dem","year":"2006","journal-title":"Blood Coagul Fibrinolysis"},{"key":"B24","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1182\/blood-2008-06-163675","article-title":"Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI","volume":"113","author":"Tucker","year":"2009","journal-title":"Blood"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1161\/ATVBAHA.113.301282","article-title":"Antithrombotic effect of antisense factor XI oligonucleotide treatment in primates","volume":"33","author":"Crosby","year":"2013","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.1182\/blood-2013-12-540872","article-title":"Selective depletion of factor XI or factor XII with antisense oligonucleotides attenuates catheter thrombosis in rabbits","volume":"123","author":"Yau","year":"2014","journal-title":"Blood"},{"key":"B27","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1055\/s-0041-1735971","article-title":"The association between factor XI deficiency and the risk of bleeding, cardiovascular, and venous thromboembolic events","volume":"122","author":"Sharman","year":"2022","journal-title":"Thromb Haemost"},{"key":"B28","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1160\/TH10-05-0307","article-title":"Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis","volume":"105","author":"Salomon","year":"2011","journal-title":"Thromb Haemost"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1002\/med.21503","article-title":"Recent advances in the discovery and development of factor XI\/XIa inhibitors","volume":"38","author":"Al-Horani","year":"2018","journal-title":"Med Res Rev"},{"key":"B30","doi-asserted-by":"publisher","first-page":"4684","DOI":"10.1182\/blood-2010-04-277798","article-title":"Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk","volume":"116","author":"Zhang","year":"2010","journal-title":"Blood"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1182\/blood-2011-10-387134","article-title":"Antisense inhibition of coagulation factor XI prolongs APTT without increased bleeding risk in cynomolgus monkeys","volume":"119","author":"Younis","year":"2012","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1056\/NEJMoa1405760","article-title":"Factor XI antisense oligonucleotide for prevention of venous thrombosis","volume":"372","author":"Buller","year":"2015","journal-title":"N Engl J Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1182\/blood-2018-10-880849","article-title":"MAA868, a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans","volume":"133","author":"Koch","year":"2019","journal-title":"Blood"},{"key":"B34","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1056\/NEJMoa2105872","article-title":"Abelacimab for prevention of venous thromboembolism","volume":"385","author":"Verhamme","year":"2021","journal-title":"N Engl J Med"},{"key":"B35","doi-asserted-by":"publisher","first-page":"4817","DOI":"10.1016\/j.jmb.2019.09.008","article-title":"Allosteric inhibition as a new mode of action for BAY 1213790, a neutralizing antibody targeting the activated form of coagulation factor XI","volume":"431","author":"Schaefer","year":"2019","journal-title":"J Mol Biol"},{"key":"B36","doi-asserted-by":"publisher","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":"Weitz","year":"2020","journal-title":"JAMA"},{"key":"B37","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1161\/ATVBAHA.119.312459","article-title":"AB023, a novel antibody that binds factor XI and blocks its activation by factor XIIa","volume":"39","author":"Chan","year":"2019","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1182\/blood.2021011725","article-title":"The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial","volume":"138","author":"Lorentz","year":"2021","journal-title":"Blood"},{"key":"B39","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1111\/cts.13148","article-title":"First-in-human study of milvexian, an oral, direct, small molecule factor XIa inhibitor","volume":"15","author":"Perera","year":"2022","journal-title":"Clin Transl Sci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2161","DOI":"10.1056\/NEJMoa2113194","article-title":"Milvexian for the prevention of venous thromboembolism","volume":"385","author":"Weitz","year":"2021","journal-title":"N Engl J Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2407","DOI":"10.1111\/jth.15439","article-title":"First evaluation of the safety, pharmacokinetics, and pharmacodynamics of BAY 2433334, a small molecule targeting coagulation factor XIa","volume":"19","author":"Thomas","year":"2021","journal-title":"J Thromb Haemost"},{"key":"B42","doi-asserted-by":"publisher","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":"Piccini","year":"2022","journal-title":"Lancet"},{"key":"B43","doi-asserted-by":"publisher","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":"Shoamanesh","year":"2022","journal-title":"Lancet"},{"key":"B44","article-title":"Bayer initiates landmark Phase III study program to investigate oral FXIa inhibitor Asundexian [EB\/OL]","author":"Jorgal","year":"2022"},{"key":"B45","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/S0140-6736(20)32658-1","article-title":"Venous thromboembolism","volume":"398","author":"Khan","year":"2021","journal-title":"Lancet"},{"key":"B46","doi-asserted-by":"publisher","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":"Ruff","year":"2014","journal-title":"Lancet"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1056\/NEJMoa1300615","article-title":"Dabigatran versus warfarin in patients with mechanical heart valves","volume":"369","author":"Eikelboom","year":"2013","journal-title":"N Engl J Med"},{"key":"B48","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1056\/NEJMoa2209051","article-title":"Rivaroxaban in rheumatic heart disease-associated atrial fibrillation","volume":"387","author":"Connolly","year":"2022","journal-title":"N Engl J Med"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2783","DOI":"10.1093\/eurheartj\/ehac242","article-title":"Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial [published correction appears in Eur Heart J. 2022 Oct 21;43(40):4194","volume":"43","author":"Collet","year":"2022","journal-title":"Eur Heart J"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1182\/blood-2018-04-848333","article-title":"Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome","volume":"132","author":"Pengo","year":"2018","journal-title":"Blood"},{"key":"B51","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ejim.2023.08.001","article-title":"A new strategy for anticoagulation: the factor XI inhibitors","volume":"116","author":"Vedovati","year":"2023","journal-title":"Eur J Intern Med"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1016\/S0140-6736(20)32439-9","article-title":"Direct oral anticoagulants: evidence and unresolved issues","volume":"396","author":"Chan","year":"2020","journal-title":"Lancet"},{"key":"B53","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/jth.15579","article-title":"A proposal for managing bleeding in patients on therapeutic factor XI(a) inhibitors","volume":"20","author":"Salomon","year":"2022","journal-title":"J Thromb Haemost"},{"key":"B54","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1007\/s40119-022-00266-6","article-title":"Effects of itraconazole and diltiazem on the pharmacokinetics and pharmacodynamics of milvexian, A factor XIa inhibitor","volume":"11","author":"Perera","year":"2022","journal-title":"Cardiol Ther"},{"key":"B55","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1161\/CIRCULATIONAHA.122.062353","article-title":"Pharmacology and clinical development of factor XI inhibitors","volume":"147","author":"Greco","year":"2023","journal-title":"Circulation"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1498826\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:43:25Z","timestamp":1748583805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1498826\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":55,"alternative-id":["10.3389\/fcvm.2025.1498826"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2025.1498826","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]},"article-number":"1498826"}}