Aetiology, secondary prevention strategies and outcomes of ischaemic stroke despite oral anticoagulant therapy in patients with atrial fibrillation

Alexandros A. Polymeris, Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
Thomas R. Meinel, Department of Neurology, Inselspital University Hospital and University of Bern, Bern, Switzerland.
Hannah Oehler, Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
Kyra Hölscher, Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
Annaelle Zietz, Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
Jan F. Scheitz, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Christian H. Nolte, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Christoph Stretz, Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Shadi Yaghi, Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Svenja Stoll, Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany.
Ruihao Wang, Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Erlangen, Germany.
Karl Georg Häusler, Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
Simon Hellwig, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Markus G. Klammer, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Simon Litmeier, Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Christopher R. Leon Guerrero, Department of Neurology, The George Washington University, Washington, DC, USA.
Iman Moeini-Naghani, Department of Neurology, The George Washington University, Washington, DC, USA.
Patrik Michel, Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Davide Strambo, Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Alexander Salerno, Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Giovanni Bianco, Stroke Center, Neurology Department, Neurocenter of Southern Switzerland EOC, Lugano, Ticino, Switzerland.
Carlo Cereda, Stroke Center, Neurology Department, Neurocenter of Southern Switzerland EOC, Lugano, Ticino, Switzerland.
Timo Uphaus, Department of Neurology, University Hospital Mainz, Mainz, Germany.
Klaus Gröschel, Department of Neurology, University Hospital Mainz, Mainz, Germany.
Mira Katan, Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
Susanne Wegener, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
Nils Peters, Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
Stefan T. Engelter, Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
Philippe A. Lyrer, Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
Leo H. Bonati, Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
Lorenz Grunder, Department of Neuroradiology, Inselspital University Hospital and University of Bern, Bern, Switzerland.
Peter Arthur Ringleb, Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.

Document Type

Journal Article

Publication Date

4-8-2022

Journal

Journal of neurology, neurosurgery, and psychiatry

DOI

10.1136/jnnp-2021-328391

Keywords

atrial fibrillation; etiology; outcome; prevention strategies; stroke despite anticoagulation

Abstract

OBJECTIVE: To investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF). METHODS: We analysed consecutive patients with AF with an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke. RESULTS: Among 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy. CONCLUSIONS: Stroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed. TRIAL REGISTRATION NUMBER: ISRCTN48292829.

Department

Neurology

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