Skip to main content
Erschienen in: InFo Neurologie + Psychiatrie 4/2024

23.04.2024 | Ischämischer Schlaganfall | Zertifizierte Fortbildung Neurologie

Antikoagulanzien

Faktor-XI-Hemmer - neue Therapeutika in der Prävention von Thromboembolien

verfasst von: Prof. Dr. med. Christian H. Nolte, Prof. Dr. med. Hans-Christoph Diener, Prof. Dr. med. Matthias Endres

Erschienen in: InFo Neurologie + Psychiatrie | Ausgabe 4/2024

zum CME-Kurs Einloggen, um Zugang zu erhalten

Auszug

Der „heilige Gral“ der Behandlung und Prävention von Thrombosen und Thromboembolien wäre ein Wirkstoff, der eine hohe Wirksamkeit (Verhinderung von Gerinnseln) und gleichzeitig ein geringes Blutungsrisiko hätte. Aus hämostasiologischer Sicht stellt die Inhibition von Faktor XI einen vielversprechenden Ansatzpunkt für die optimale Thromboembolieprävention dar, denn ein erniedrigter Spiegel von Faktor XI schützt vor Thrombosen, ohne das spontane Blutungsrisiko wesentlich zu erhöhen. Momentan werden in der Faktor-XIa-Inhibition Medikamente aus drei Wirkstoffklassen klinisch getestet. Dieser Artikel gibt eine Übersicht zur Studienlage aller drei Substanzklassen.
Literatur
1.
Zurück zum Zitat Fredenburgh JC, Weitz JL. Factor XI as a target for new anticoagulants. Hamostasiologie. 2021;41:104-110 Fredenburgh JC, Weitz JL. Factor XI as a target for new anticoagulants. Hamostasiologie. 2021;41:104-110
2.
Zurück zum Zitat Deitelzweig S et al. Comparison of major bleeding risk in patients with non-valvular atrial fibrillation receiving direct oral anticoagulants in the real-world setting: a network meta-analysis. Curr Med Res Opin. 2017:1-12 Deitelzweig S et al. Comparison of major bleeding risk in patients with non-valvular atrial fibrillation receiving direct oral anticoagulants in the real-world setting: a network meta-analysis. Curr Med Res Opin. 2017:1-12
3.
Zurück zum Zitat Gigante B, Ten Cate H. Factor XI inhibitors in patients with cardiovascular disease and a high risk of bleeding: a cautionary tale. Nat Rev Cardiol. 2023;20(8):511-2 Gigante B, Ten Cate H. Factor XI inhibitors in patients with cardiovascular disease and a high risk of bleeding: a cautionary tale. Nat Rev Cardiol. 2023;20(8):511-2
4.
Zurück zum Zitat Wang X et al. Effects of factor IX and XI deficiency on ferric chloride-induced carotd artery occlusion in mice. J Thromb Heaemost. 2005;3:695-702 Wang X et al. Effects of factor IX and XI deficiency on ferric chloride-induced carotd artery occlusion in mice. J Thromb Heaemost. 2005;3:695-702
5.
Zurück zum Zitat Puy C et al. The hemostatic role of factor XI. Thromb Res. 2016;141:8-11 Puy C et al. The hemostatic role of factor XI. Thromb Res. 2016;141:8-11
6.
Zurück zum Zitat Sharman Moser S et al. The association between Factor XI deficiency and the risk of bleeding cardiocavcular and venous thromboembolich events. Thromb Haemost. 2022;122;808-17 Sharman Moser S et al. The association between Factor XI deficiency and the risk of bleeding cardiocavcular and venous thromboembolich events. Thromb Haemost. 2022;122;808-17
7.
Zurück zum Zitat Georg B et al. Leveraging human genetics to estimate clinical risk reductions achievable by inhibiting factor XI. Stroke. 2019;50:3004-12 Georg B et al. Leveraging human genetics to estimate clinical risk reductions achievable by inhibiting factor XI. Stroke. 2019;50:3004-12
8.
Zurück zum Zitat Fredenburg JC et al. News at XI: moving beyond factor Xa inhibitors. J Thromb Haemost. 2023;21:1692-702 Fredenburg JC et al. News at XI: moving beyond factor Xa inhibitors. J Thromb Haemost. 2023;21:1692-702
9.
Zurück zum Zitat Canovi S et al. Hereditary coagulation factor XI deficiency: a rare or neglected disease? Results from a retrospective, single-centre cohort in northern Italy. Blood Coagul Fibrinolysis. 2024;35(1):32-36 Canovi S et al. Hereditary coagulation factor XI deficiency: a rare or neglected disease? Results from a retrospective, single-centre cohort in northern Italy. Blood Coagul Fibrinolysis. 2024;35(1):32-36
10.
Zurück zum Zitat Weitz JL, Fredenburgh JC. Factors XI nd XII as targets for new anticoagulants. Front Med (Lausanne). 2017;4:19 Weitz JL, Fredenburgh JC. Factors XI nd XII as targets for new anticoagulants. Front Med (Lausanne). 2017;4:19
11.
Zurück zum Zitat Koch AV et al. MAA868 a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans. Blood. 2019;133:1507-15 Koch AV et al. MAA868 a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans. Blood. 2019;133:1507-15
12.
Zurück zum Zitat Verhamme P et al. Abelacimab for prevention of venous thromboembolism. N Engl J Med. 2021;385:609-17 Verhamme P et al. Abelacimab for prevention of venous thromboembolism. N Engl J Med. 2021;385:609-17
15.
Zurück zum Zitat Weitz Jl et al. Effect of osocimab in preventing venous thromboembolism among patients undergoing knee arthoplasty; the FOXTROT randomized clinical trial. JAMA. 2020;323:130-9 Weitz Jl et al. Effect of osocimab in preventing venous thromboembolism among patients undergoing knee arthoplasty; the FOXTROT randomized clinical trial. JAMA. 2020;323:130-9
16.
Zurück zum Zitat Lorentz CU et al. The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial. Blood. 2021;138:2173-84 Lorentz CU et al. The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial. Blood. 2021;138:2173-84
17.
Zurück zum Zitat Piccini JP et al. Safety of the oral factor Xia inhibitor asundexian compared with apixaban in patients with atrial fibrillations (PACIFIC AF): a mulcicentre randomized double blind double dummy dose-finding phase 2 study. Lancet. 2022;399:1383-90 Piccini JP et al. Safety of the oral factor Xia inhibitor asundexian compared with apixaban in patients with atrial fibrillations (PACIFIC AF): a mulcicentre randomized double blind double dummy dose-finding phase 2 study. Lancet. 2022;399:1383-90
18.
Zurück zum Zitat Rao SV et al. 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. 2022;146:1196-206 Rao SV et al. 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. 2022;146:1196-206
19.
Zurück zum Zitat Shoamanesh A et al. Factor Xi inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international randomized, double-blind, placebo-controlled, phase 2b trial. Lancet. 2022;400:997-1107 Shoamanesh A et al. Factor Xi inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international randomized, double-blind, placebo-controlled, phase 2b trial. Lancet. 2022;400:997-1107
20.
Zurück zum Zitat Smith EE et al. Effect of the Factor XIa Inhibitor Asundexian According to Baseline Infarct Pattern and on MRI Covert Infarct Outcomes Stroke. 2024;55(2):392-402 Smith EE et al. Effect of the Factor XIa Inhibitor Asundexian According to Baseline Infarct Pattern and on MRI Covert Infarct Outcomes Stroke. 2024;55(2):392-402
21.
Zurück zum Zitat Eikelboom JW et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017;377:1319-30 Eikelboom JW et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017;377:1319-30
23.
Zurück zum Zitat Perera V et al. Single-dose pharmacokinetics of milvexian in participants with mild or moderate hepatic impairment compared to healthy participants. Clin Pharmacokinet. 2022;61:857-67 Perera V et al. Single-dose pharmacokinetics of milvexian in participants with mild or moderate hepatic impairment compared to healthy participants. Clin Pharmacokinet. 2022;61:857-67
24.
Zurück zum Zitat Weitz JI et al. Milvexian for the Prevention of Venous Thromboembolism. N Engl J Med. 2021;385:2161-72 Weitz JI et al. Milvexian for the Prevention of Venous Thromboembolism. N Engl J Med. 2021;385:2161-72
25.
Zurück zum Zitat Sharma M et al. 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. 2024;23(1):46-59 Sharma M et al. 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. 2024;23(1):46-59
26.
Zurück zum Zitat Croke ST et al. Antisense technology: a review. J Biol Chem 2021;296:100416 Croke ST et al. Antisense technology: a review. J Biol Chem 2021;296:100416
27.
Zurück zum Zitat Büller HR et al. Faktor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med. 2015;372:232-40 Büller HR et al. Faktor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med. 2015;372:232-40
28.
Zurück zum Zitat Walsh M ert al. Phase 2 Study of the Factor XI Antisense Inhibitor IONIS-FXIRx in Patients With ESRD. Kidney Int Rep. 2021;7:200-9 Walsh M ert al. Phase 2 Study of the Factor XI Antisense Inhibitor IONIS-FXIRx in Patients With ESRD. Kidney Int Rep. 2021;7:200-9
Metadaten
Titel
Antikoagulanzien
Faktor-XI-Hemmer - neue Therapeutika in der Prävention von Thromboembolien
verfasst von
Prof. Dr. med. Christian H. Nolte
Prof. Dr. med. Hans-Christoph Diener
Prof. Dr. med. Matthias Endres
Publikationsdatum
23.04.2024
Verlag
Springer Medizin
Erschienen in
InFo Neurologie + Psychiatrie / Ausgabe 4/2024
Print ISSN: 1437-062X
Elektronische ISSN: 2195-5166
DOI
https://doi.org/10.1007/s15005-024-3889-8

Weitere Artikel der Ausgabe 4/2024

InFo Neurologie + Psychiatrie 4/2024 Zur Ausgabe