• Stuart J Connolly, Mukul Sharma, Alexander T Cohen, Andrew M Demchuk, Anna Członkowska, Arne G Lindgren, Carlos A Molina, Daniel Bereczki, Danilo Toni, David J Seiffge, David Tanne, Else Charlotte Sandset, Georgios Tsivgoulis, Hanne Christensen, Jan Beyer-Westendorf, Jonathan M Coutinho, Mark Crowther, Peter Verhamme, Pierre Amarenco, Risto O Roine, Robert Mikulik, Robin Lemmens, Roland Veltkamp, Saskia Middeldorp, Thompson G Robinson, Truman John Milling, Vitor Tedim-Cruz, Wilfried Lang, Anders Himmelmann, Per Ladenvall, Mikael Knutsson, Ella Ekholm, Andrew Law, Amanda Taylor, Tetyana Karyakina, Lizhen Xu, Kate Tsiplova, Sven Poli, Bernd Kallmünzer, Christoph Gumbinger, Ashkan Shoamanesh, and ANNEXA-I Investigators.
• From the Population Health Research Institute, McMaster University, Hamilton, ON (S.J.C., M.S., M.C., A.T., T.K., L.X., K.T., A.S.), and the Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB (A.M.D.) - both in Canada; Guy's and St. Thomas' Hospital, King's College London (A.T.C.), and Imperial College (R.V.), London, NIHR Biomedical Research Centre and College of Life Sciences, University of Leicester, Leicester (T.G.R.), and Alexion Pharmaceuticals UK, Uxbridge (A.L.) - all in the United Kingdom; the Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland (A.C.); the Department of Clinical Sciences Lund, Neurology, Lund University, and the Department of Neurology, Skåne University Hospital, Lund (A.G.L.), and AstraZeneca Biopharmaceuticals Research and Development, Late-stage Development, Cardiovascular, Renal, and Metabolism, Gothenburg (A.H., P.L., M.K., E.E.) - all in Sweden; Vall d'Hebron University Hospital, Barcelona (C.A.M.); Semmelweis University, Budapest, Hungary (D.B.); Sapienza University of Rome, Rome (D. Toni); the Department of Neurology, Inselspital University Hospital and University of Bern, Bern, Switzerland (D.J.S.); Rambam Health Care Campus, Technion, Israel Institute of Technology, Haifa (D. Tanne); the Department of Neurology, Oslo University Hospital, and the Norwegian Air Ambulance Foundation - both in Oslo (E.C.S.); the Second Department of Neurology, National and Kapodistrian University of Athens, "Attikon" University Hospital, Athens (G.T.); Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen (H.C.); the Department of Medicine 1, Division "Thrombosis and Hemostasis," University Hospital Dresden, Dresden (J.B.-W.), Alfried Krupp Krankenhaus, Essen (R.V.), the Department of Neurology and Stroke (S.P.) and the Hertie Institute for Clinical Brain Research (S.P.), Eberhard-Karls University, Tübingen, the Department of Neurology, Universitätsklinikum Erlangen, Erlangen (B.K.), and the Department of Neurology, Heidelberg University Hospital, Heidelberg (C.G.) - all in Germany; the Department of Neurology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (J.M.C.), and Radboud University Medical Center, Nijmegen (S.M.) - both in the Netherlands; University Hospitals Leuven, University of Leuven (P.V.), the Department of Neurosciences and Experimental Neurology, KU Leuven (R.L.), and the Department of Neurology, University Hospitals Leuven (R.L.) - all in Leuven, Belgium; Bichat Claude-Bernard Hospital, Paris (P.A.); Turku University Hospital, Turku, Finland (R.O.R.); Tomas Bata Regional Hospital, Zlín, Czech Republic (R.M.); Dell Medical School, University of Texas, Austin, and the University of Houston, Houston (T.J.M.); University of Porto, Porto, Portugal (V.T.-C.); and Hospital of St. John of God, Sigmund Freud University, Medical Faculty, Vienna (W.L.).
• N. Engl. J. Med. 2024 May 16; 390 (19): 174517551745-1755.

BackgroundPatients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied.MethodsWe randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death.ResultsA total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days.ConclusionsAmong patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).Copyright © 2024 Massachusetts Medical Society.

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