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

• Published in: Lancet neurology 2024-01, Vol.23 (1), p.46-59
• Main Authors: Sharma, Mukul, Molina, Carlos A, Toyoda, Kazunori, Bereczki, Daniel, Bangdiwala, Shrikant I, Kasner, Scott E, Lutsep, Helmi L, Tsivgoulis, Georgios, Ntaios, George, Czlonkowska, Anna, Shuaib, Ashfaq, Amarenco, Pierre, Endres, Matthias, Yoon, Byung-Woo, Tanne, David, Toni, Danilo, Yperzeele, Laetitia, von Weitzel-Mudersbach, Paul, Sampaio Silva, Gisele, Avezum, Alvaro, Dawson, Jesse, Strbian, Daniel, Tatlisumak, Turgut, Eckstein, Jens, Ameriso, Sebastián F, Weber, Joerg R, Sandset, Else Charlotte, Goar Pogosova, Nana, Lavados, Pablo M, Arauz, Antonio, Gailani, David, Diener, Hans-Christoph, Bernstein, Richard A, Cordonnier, Charlotte, Kahl, Anja, Abelian, Grigor, Donovan, Mark, Pachai, Chahin, Li, Danshi, Hankey, Graeme J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anticoagulants; Antiplatelet therapy; Aspirin; Atherosclerosis; Bleeding; Blood clots; Brain Ischemia - drug therapy; Brain Ischemia - prevention & control; Brain research; Cerebral infarction; Clinical trials; Clopidogrel; Coagulation factors; Double-Blind Method; Factor XI deficiency; Factor XIa; Female; Hemorrhage - chemically induced; Hemorrhage - drug therapy; Humans; Ischemia; Ischemic Attack, Transient - drug therapy; Ischemic Stroke - drug therapy; Joint replacement surgery; Life Sciences; Magnetic resonance imaging; Male; Medical imaging; Middle Aged; Neuroimaging; Patients; Placebos; Prevention; Stroke; Stroke - drug therapy; Stroke - prevention & control; Thromboembolism; Thrombosis; Transient ischemic attack; Treatment Outcome
• ISSN: 1474-4422; 1474-4465; 1474-4465
• DOI: 10.1016/S1474-4422(23)00403-9

People with factor XI deficiency have lower rates of ischaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA). AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (