Piccini JP, Caso V, Connolly SJ, Fox KAA, Oldgren J, Jones WS, Gorog DA, Durdil V, Viethen T, Neumann C, Mundl H, Patel MR (2022) 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. Lancet 399(10333):1383–1390. https://doi.org/10.1016/s0140-6736(22)00456-1

Article  CAS  PubMed  Google Scholar 

Walsh M, Bethune C, Smyth A, Tyrwhitt J, Jung SW, Yu RZ, Wang Y, Geary RS, Weitz J, Bhanot S (2022) Phase 2 study of the factor XI antisense inhibitor IONIS-FXI(rx) in patients with ESRD. Kidney Int Rep 7(2):200–209. https://doi.org/10.1016/j.ekir.2021.11.011

Article  PubMed  Google Scholar 

Lorentz CU, Tucker EI, Verbout NG, Shatzel JJ, Olson SR, Markway BD, Wallisch M, Ralle M, Hinds MT, McCarty OJT, Gailani D, Weitz JI, Gruber A (2021) The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial. Blood 138(22):2173–2184. https://doi.org/10.1182/blood.2021011725

Article  CAS  PubMed  PubMed Central  Google Scholar 

Verhamme P, Yi BA, Segers A, Salter J, Bloomfield D, Büller HR, Raskob GE, Weitz JI (2021) Abelacimab for Prevention of venous thromboembolism. N Engl J Med 385(7):609–617. https://doi.org/10.1056/NEJMoa2105872

Article  CAS  PubMed  Google Scholar 

Büller HR, Bethune C, Bhanot S, Gailani D, Monia BP, Raskob GE, Segers A, Verhamme P, Weitz JI (2015) Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med 372(3):232–240. https://doi.org/10.1056/NEJMoa1405760

Article  CAS  PubMed  Google Scholar 

Weitz JI, Bauersachs R, Becker B, Berkowitz SD, Freitas MCS, Lassen MR, Metzig C, Raskob GE (2020) Effect of Osocimab in preventing venous thromboembolism among patients undergoing knee arthroplasty: the FOXTROT Randomized Clinical Trial. JAMA 323(2):130–139. https://doi.org/10.1001/jama.2019.20687

Article  CAS  PubMed  PubMed Central  Google Scholar 

Weitz JI, Strony J, Ageno W, Gailani D, Hylek EM, Lassen MR, Mahaffey KW, Notani RS, Roberts R, Segers A, Raskob GE (2021) Milvexian for the Prevention of venous thromboembolism. N Engl J Med 385(23):2161–2172. https://doi.org/10.1056/NEJMoa2113194

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shoamanesh A, Mundl H, Smith EE, Masjuan J, Milanov I, Hirano T, Agafina A, Campbell B, Caso V, Mas JL, Dong Q, Turcani P, Christensen H, Ferro JM, Veltkamp R, Mikulik R, De Marchis GM, Robinson T, Lemmens R, Hart RG (2022) Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet 400(10357):997–1007. https://doi.org/10.1016/s0140-6736(22)01588-4

Article  CAS  PubMed  Google Scholar 

Sharma M, Molina CA, Toyoda K, Bereczki D, Bangdiwala SI, Kasner SE, Lutsep HL, Tsivgoulis G, Ntaios G, Czlonkowska A, Shuaib A, Amarenco P, Endres M, Yoon BW, Tanne D, Toni D, Yperzeele L, von Weitzel-Mudersbach P, Silva S, Hankey G, G. J (2024) Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial. Lancet Neurol 23(1):46–59. https://doi.org/10.1016/s1474-4422(23)00403-9

Article  CAS  PubMed  Google Scholar 

Rao SV, Kirsch B, Bhatt DL, Budaj A, Coppolecchia R, Eikelboom J, James SK, Jones WS, Merkely B, Keller L, Hermanides RS, Campo G, Ferreiro JL, Shibasaki T, Mundl H, Alexander JH (2022) 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. Circulation 146(16):1196–1206. https://doi.org/10.1161/circulationaha.122.061612

Article  CAS  PubMed  Google Scholar 

Chen A, Stecker E, B AW (2020) Direct oral anticoagulant use: a practical guide to Common Clinical challenges. J Am Heart Assoc 9(13):e017559. https://doi.org/10.1161/jaha.120.017559

Article  CAS  PubMed  PubMed Central  Google Scholar 

Greco A, Laudani C, Spagnolo M, Agnello F, Faro DC, Finocchiaro S, Legnazzi M, Mauro MS, Mazzone PM, Occhipinti G, Rochira C, Scalia L, Capodanno D (2023) Pharmacology and Clinical Development of factor XI inhibitors. Circulation 147(11):897–913. https://doi.org/10.1161/circulationaha.122.062353

Article  CAS  PubMed  Google Scholar 

Ali AE, Becker RC (2024) Factor XI: structure, function and therapeutic inhibition. Journal of thrombosis and thrombolysis. https://doi.org/10.1007/s11239-024-02972-5

Hsu C, Hutt E, Bloomfield DM, Gailani D, Weitz JI (2021) Factor XI inhibition to uncouple thrombosis from hemostasis: JACC Review topic of the Week. J Am Coll Cardiol 78(6):625–631. https://doi.org/10.1016/j.jacc.2021.06.010

Article  CAS  PubMed  PubMed Central  Google Scholar 

Salomon O, Steinberg DM, Koren-Morag N, Tanne D, Seligsohn U (2008) Reduced incidence of ischemic stroke in patients with severe factor XI deficiency. Blood 111(8):4113–4117. https://doi.org/10.1182/blood-2007-10-120139

Article  CAS  PubMed  Google Scholar 

Preis M, Hirsch J, Kotler A, Zoabi A, Stein N, Rennert G, Saliba W (2017) Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events. Blood 129(9):1210–1215. https://doi.org/10.1182/blood-2016-09-742262

Article  CAS  PubMed  Google Scholar 

Salomon O, Steinberg DM, Zucker M, Varon D, Zivelin A, Seligsohn U (2011) Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis. Thromb Haemost 105(2):269–273. https://doi.org/10.1160/th10-05-0307

Article  CAS  PubMed  Google Scholar 

Daghlas I, Gill D (2023) Leveraging genetic predictors of factor XI levels to anticipate results from clinical trials. Eur J Neurol 30(7):2112–2116. https://doi.org/10.1111/ene.15820

Article  PubMed  Google Scholar 

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, Moher D (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71

Article  PubMed  PubMed Central  Google Scholar 

Mourad, Ouzzani Hossam, Hammady Zbys, Fedorowicz Ahmed, Elmagarmid (2016) Rayyan—a web and mobile app for systematic reviews Systematic Reviews 5(1) https://doi.org/10.1186/s13643-016-0384-4

Chapter 8 Assessing risk of bias in a randomized trial | Cochrane Training. https://training.cochrane.org/handbook/current/chapter-08

Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G (2012) Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis. Pract Guidelines Chest 141(2 Suppl). 9th edn.https://doi.org/10.1378/chest.11-2292. American College of Chest Physicians Evidence-Based Clinicale44S-e88S

Zirlik A, Bode C (2017) Vitamin K antagonists: relative strengths and weaknesses vs. direct oral anticoagulants for stroke prevention in patients with atrial fibrillation. J Thromb Thrombolysis 43(3):365–379. https://doi.org/10.1007/s11239-016-1446-0

Article  CAS  PubMed  Google Scholar 

Hinojar R, Jiménez-Natcher JJ, Fernández-Golfín C, Zamorano JL (2015) New oral anticoagulants: a practical guide for physicians. Eur Heart J Cardiovasc Pharmacother 1(2):134–145. https://doi.org/10.1093/ehjcvp/pvv002

Article  PubMed  Google Scholar 

Woodruff RS, Sullenger B, Becker RC (2011) The many faces of the contact pathway and their role in thrombosis. J Thromb Thrombolysis 32(1):9–20. https://doi.org/10.1007/s11239-011-0578-5

Article  PubMed  Google Scholar 

Meijers JC, Tekelenburg WL, Bouma BN, Bertina RM, Rosendaal FR (2000) High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med 342(10):696–701. https://doi.org/10.1056/nejm200003093421004

Article  CAS  PubMed  Google Scholar 

Kyrle PA, Eischer L, Šinkovec H, Eichinger S (2019) Factor XI and recurrent venous thrombosis: an observational cohort study. J Thromb Haemost 17(5):782–786. https://doi.org/10.1111/jth.14415

Article  PubMed  Google Scholar 

Presume J, Ferreira J, Ribeiras R, Mendes M (2022) 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. J Thromb Haemost 20(12):2930–2938. https://doi.org/10.1111/jth.15890

Article  CAS  PubMed  PubMed Central  Google Scholar 

Galli M, Laborante R, Ortega-Paz L, Franchi F, Rollini F, D’Amario D, Capodanno D, Tremoli E, Gibson CM, Mehran R, Angiolillo DJ (2023) Factor XI inhibitors in early clinical trials: a Meta-analysis. Thromb Haemost 123(6):576–584. https://doi.org/10.1055/a-2043-0346

Article  PubMed  Google Scholar