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Published on: September 17, 2014
Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source.
Robert G Hart1, Mukul Sharma1, Hardi Mundl1
1From the Departments of Medicine-Neurology (R.G.H., M.S., A.S.), Health Research Methods, Evidence, and Impact (S.I.B.), Pathology and Molecular Medicine (G. Pare), and Medicine-Cardiology (S.J.C.), Population Health Research Institute (B.S., P.S., E.T.), and the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W.), Hamilton, ON, the Vancouver Stroke Program, University of British Columbia, Vancouver (O.R.B.), and Sunnybrook Health Sciences Centre, University of Toronto, Toronto (C.J.) - all in Canada; Bayer, Wuppertal (H.M.), Klinik für Neurologie, Charité-Universitätsmedizin Berlin (M.E.), and Bayer (B.K.), Berlin, and Bayer, Leverkusen (C.P.) - all in Germany; the Department of Neurology, University of Pennsylvania, Philadelphia (S.E.K.), and Janssen Research and Development, Spring House (G. Peters) - both in Pennsylvania; Bayer U.S., Pharmaceuticals Clinical Development Thrombosis, Whippany, NJ (S.D.B.); Clínica Alemana de Santiago, Santiago, Chile (P.L.); the Department of Neurology and Stroke Center, Beijing Tiantan Hospital, Beijing (Yongjun Wang, Yilong Wang); Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona (A.D.); Pirogov Russian National Research Medical University, Moscow (N.S.); International Clinical Research Center and Neurology Department, St. Anne's University Hospital, Brno, Czech Republic (R.M.); Centro Hospitalar e Universitário de Coimbra, Hospitais da Universidade de Coimbra, Coimbra, Portugal (L.C.); the Department of Clinical Sciences (Neurology), Lund University, and the Department of Neurology and Rehabilitation Medicine, Skåne University Hospital, Lund (A.L.), and the Department of Clinical Neuroscience-Neurology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg (T.T.) - all in Sweden; Instituto Nacional de Neurología y Neurocirugía, Mexico City (A.A.); Hospital St. John of God, Sigmund Freud Private University, Medical Faculty, Vienna (W.L.); the 2nd Department of Neurology, Institute of Psychiatry and Neurology, and the Department of Pharmacology, Medical University of Warsaw, Warsaw, Poland (A.C.); the Department of Internal Medicine, University Hospital Basel, Basel, Switzerland (J.E.); Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo (R.J.G.); Assistance Publique-Hôpitaux de Paris, Bichat Hospital, Paris-Diderot, Sorbonne Paris Cité University, Paris (P.A.); Institute for Neurological Research-Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Buenos Aires (S.F.A.); the Department of Neurology, Helsinki University Central Hospital, Helsinki (T.T.); Imperial College London, London (R.V.); Medical School, University of Western Australia, and Sir Charles Gairdner Hospital, Perth, Australia (G.J.H.); the Department of Human Neurosciences, Sapienza University of Rome, Rome (D.T.); the Department of Neurology, Semmelweis University, Budapest, Hungary (D.B.); International University of Health and Welfare, Sanno Hospital and Sanno Medical Center, Tokyo (S.U.); the Department of Medicine, University of Thessaly, Larissa, Greece (G.N.); Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea (B.-W.Y.); the Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels (R.B.); the Department of Neurology, ZorgSaam Hospital, Terneuzen, the Netherlands (R.B.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom (K.W.M.); Shaare Zedek Medical Center, Jerusalem (N.B.); the Department of Neurology, Selcuk University, Konya, Turkey (S.O.); Health Research Board Clinical Research Facility, National University of Ireland, Galway (M.J.O.); Tiervlei Trial Centre and Head of Internal Medicine Karl Bremer Hospital, Bellville, South Africa (M.M.D.V.B.); and Baylor College of Medicine, Houston (W.F.P.).
Rivaroxaban did not outperform aspirin in preventing recurrent strokes from undetermined sources. The study found rivaroxaban was associated with a significantly higher risk of major bleeding events.
Area of Science:
- Neurology
- Cardiology
- Pharmacology
Background:
- Embolic strokes of undetermined source (ESUS) constitute 20% of ischemic strokes, carrying a high recurrence risk.
- Oral factor Xa inhibitors like rivaroxaban are being investigated as alternatives to aspirin for secondary stroke prevention.
Purpose of the Study:
- To compare the efficacy and safety of rivaroxaban (15 mg daily) versus aspirin (100 mg daily) in preventing recurrent stroke in ESUS patients.
- To evaluate the primary efficacy outcome of recurrent stroke or systemic embolism and the primary safety outcome of major bleeding.
Main Methods:
- A randomized trial involving 7213 participants across 459 sites.
- Patients with recent ischemic stroke presumed to be ESUS were assigned to either rivaroxaban or aspirin.
- Follow-up was conducted for a median of 11 months, with early termination due to bleeding concerns and lack of efficacy.
Main Results:
- The primary efficacy outcome occurred at similar rates in both groups (5.1% for rivaroxaban vs. 4.8% for aspirin), showing no significant difference (HR, 1.07; P=0.52).
- Recurrent ischemic stroke rates were also comparable (4.7% for both groups).
- Major bleeding occurred significantly more often in the rivaroxaban group (1.8% vs. 0.7% for aspirin; HR, 2.72; P<0.001).
Conclusions:
- Rivaroxaban is not superior to aspirin for preventing recurrent stroke in patients with embolic stroke of undetermined source.
- Rivaroxaban use was associated with a substantially increased risk of major bleeding compared to aspirin.
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