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Publications

Journal Article Ahead of print

PubMed: 42866879 DOI: 10.1161/CIRCULATIONAHA.126.081836

Bleeding With Asundexian Versus Placebo in Patients With Noncardioembolic Ischemic Stroke or High-Risk TIA: OCEANIC-STROKE Randomized Trial.

Circulation

Authors: John W Eikelboom, Lizhen Xu, Ashkan Shoamanesh, Qiang Dong, Teruyuki Hirano, Jeffrey L Saver, Jaime Masjuan, Andrew M Demchuk, Charlotte Cordonnier, Daniel Bereczki, Georgios Tsivgoulis, Roland Veltkamp, Ivan Staikov, Hee-Joon Bae, Bruce C V Campbell, Andrea Zini, I-Hui Lee, Martin Kovář, Robert Mikulik, Robin Lemmens, José M Ferro, Thompson Robinson, Hanne Christensen, Serefnur Ozturk, Ronen R Leker, Peter Turcani, Agnieszka Slowik, Pablo Amaya, Fan Kee Hoo, Gian Marco De Marchis, Michael Knoflach, P N Sylaja, Jukka Putaala, Jonathan M Coutinho, H Bart van der Worp, Evija Miglane, Vaidas Matijošaitis, Arne G Lindgren, Gisele Sampaio Silva, Else Charlotte Sandset, Saule T Turuspekova, Pablo Colorado, Scott E Kasner, Lars Keller, Christoph Neumann, Eva Muehlhofer, Helle Klingenberg Iversen, Yolanda Silva, Oscar Ayo-Martín, Ashfaq Shuaib … and 4 other authors

Affiliations

  • Population Health Research Institute, Hamilton Health Sciences, McMaster University, Canada (J.W.E. L.X. A. Shoamanesh, K.S. R.A.J. M.S.).
  • Huashan Hospital Fudan University, Shanghai, China (Q.D.).
  • Department of Stroke and Cerebrovascular Medicine, Kyorin University School of Medicine, Shinkawa, Japan (T.H.).
  • David Geffen School of Medicine, University of California-Los Angeles (J.L.S.).
  • Hospital Universitario Ramón y Cajal, Madrid, Spain (J.M.).
  • University of Calgary, Canada (A.M.D.).
  • University of Lille, Inserm, CHU Lille, France (C.C.).
  • Semmelweis University, Budapest, Hungary (D.B.).
  • Second Department of Neurology, National and Kapodistrian University of Athens, School of Medicine, "Attikon" University Hospital, Athens, Greece (G.T.).
  • Department of Neurology, Alfried Krupp Krankenhaus Essen, Germany (R.V.).
  • Department of Brain Sciences, Imperial College London, United Kingdom (R.V.).
  • Department of Neurology, University Hospital Heidelberg, Germany (R.V.).
  • Department of Neurology, Acibadem City Clinic University Hospital Tokuda, Sofia, Bulgaria (I.S.).
  • Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea (H.-J.B.).
  • Department of Medicine and Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia (B.C.V.C.).
  • IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy (A.Z.).
  • Taipei Veterans General Hospital, Taipei City, Taiwan (I-H.L.).
  • National Yang Ming Chiao Tung University, Taipei City, Taiwan (I-H.L.).
  • Na Homolce Hospital, Prague, Czechia (M. Kovář).
  • St Anne's University Hospital Brno, Czechia (R.M.).
  • UZ Leuven, Belgium (R.L.).
  • CHLN, Lisbon, Portugal (J.M.F.).
  • University of Leicester, United Kingdom (T.R.).
  • Copenhagen University Hospital, Bispebjerg, Denmark (H.C.).
  • Faculty of Medicine, Department of Neurology, Neurointensive Care, Stroke Center, Selcuk Universitesi, Konya, Turkey (S.O.).
  • Department of Neurology, Stroke Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel (R.R.L.).
  • 1st Department of Neurology, Comenius University in Bratislava, Slovakia (P.T.).
  • Department of Neurology, Jagiellonian University, Medical College, Krakow, Poland (A. Slowik).
  • Fundacion Valle del Lili, Cali, Colombia (P.A.).
  • Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra, Malaysia (F.K.H.).
  • University Research and Teaching Hospital, HOCH-Kantonsspital St Gallen, Switzerland (G.M.D.M.).
  • Medical University of Innsbruck, Austria (M. Knoflach).
  • Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India (P.N.S.).
  • Department of Neurology, University of Helsinki and Helsinki University Hospital, Finland (J.P.).
  • Amsterdam University Medical Center, The Netherlands (J.M.C.).
  • University Medical Center Utrecht, The Netherlands (J.B.v.d.W.).
  • P. Stradins Clinical University Hospital and Riga Stradins University, Department of Neurology and Neurosurgery, Latvia (E. Miglane).
  • Lithuanian University of Health Sciences, Kaunas (V.M.).
  • Department of Clinical Sciences Lund, Neurology, Lund University, Sweden (A.G.L.).
  • Department of Neurology, Skåne University Hospital, Lund, Sweden (A.G.L.).
  • Universidade Federal de São Paulo, Brazil (G.S.S.).
  • Hospital Israelita Albert Einstein, São Paulo, Brazil (G.S.S.).
  • Oslo University Hospital, Norway (E.C.S.).
  • Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan (S.T.T.).
  • Bayer AG, Whippany, NJ (P.C. S.E.K.).
  • Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (S.E.K.).
  • Bayer AG, Wuppertal, Germany (L.K. C.N. E. Muehlhofer).
  • Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Denmark (H.K.I.).
  • Neurology Department, Hospital Universitari Dr Josep Trueta, IDIBGI, Girona, Spain (Y.S.).
  • Complejo Hospitalario Universitario de Albacete, Universidad de Castilla-La Mancha, Spain (O.A.-M.).
  • Division of Neurology, University of Alberta, Edmonton, Canada (A. Shuaib).

Abstract

BACKGROUND

OCEANIC-STROKE (XXX) showed that asundexian added to antiplatelet therapy reduced ischemic stroke without significantly increasing bleeding in patients with noncardioembolic ischemic stroke or high-risk transient ischemic attack. We characterized bleeding categories, sites, and key subgroups.

METHODS

In the safety population, 12 254 participants received at least 1 dose of asundexian (n=6124) or placebo (n=6130). Bleeding was categorized by International Society on Thrombosis and Haemostasis criteria as major, clinically relevant nonmajor (CRNM), or minor. While-on-treatment analyses included events through 2 days after the last dose, with death and permanent discontinuation as competing risks.

RESULTS

Major bleeding occurred in 117 (1.9%) participants with asundexian and 107 (1.7%) with placebo (cause-specific hazard ratio [csHR], 1.10 [95% CI, 0.85-1.44]; P=0.46). Major or CRNM bleeding occurred in 339 (5.5%) and 307 (5.0%), respectively (csHR, 1.12 [95% CI, 0.96-1.30]; P=0.16), and any bleeding in 763 (12.5%) and 752 (12.3%) (csHR, 1.02 [95% CI, 0.93-1.13]; P=0.65). Treatment effects for major and major or CRNM bleeding were consistent across prespecified subgroups, including planned dual antiplatelet therapy. Symptomatic intracranial hemorrhage occurred in 41 (0.7%) and 36 (0.6%) participants. Any gastrointestinal bleeding occurred in 186 (3.0%) and 147 (2.4%) (csHR, 1.28 [95% CI, 1.03-1.59]), and lower gastrointestinal bleeding in 102 (1.7%) and 59 (1.0%) (csHR, 1.75 [95% CI, 1.27-2.41]), primarily rectal bleeding. Any procedure-related bleeding and any mucosal bleeding did not differ significantly.

CONCLUSIONS

Asundexian added to antiplatelet therapy reduced ischemic stroke without significantly increasing major, major or CRNM, or any bleeding. Lower gastrointestinal bleeding was more frequent with asundexian, whereas treatment effects on major and major or CRNM bleeding were consistent across prespecified subgroups.

REGISTRATION

URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05686070.

MeSH

Hemorrhage, Ischemic Stroke, Stroke, Cardiovascular System, Therapeutics, Blood Circulation