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

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.

• Authors: Alexandros A Polymeris, Thomas R Meinel, Hannah Oehler, Kyra Hölscher, Annaelle Zietz, Jan F Scheitz, Christian H Nolte, Christoph Stretz, Shadi Yaghi, Svenja Stoll, Ruihao Wang, Karl Georg Häusler, Simon Hellwig, Markus G Klammer, Simon Litmeier, Christopher R Leon Guerrero, Iman Moeini-Naghani, Patrik Michel, Davide Strambo, Alexander Salerno, Giovanni Bianco, Carlo Cereda, Timo Uphaus, Klaus Gröschel, Mira Katan, Susanne Wegener, Nils Peters, Stefan T Engelter, Philippe A Lyrer, Leo H Bonati, Lorenz Grunder, Peter Arthur Ringleb, Urs Fischer, Bernd Kallmünzer, Jan C Purrucker, David J Seiffge
• Journal: Journal of neurology, neurosurgery, and psychiatry (J Neurol Neurosurg Psychiatry) Vol. 93 Issue 6 Pg. 588-598 (06 2022) ISSN: 1468-330X [Electronic] England
• PMID: 35396339 (Publication Type: Journal Article)
• Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Anticoagulants

Topics

• Administration, Oral
• Aged, 80 and over
• Anticoagulants (adverse effects)
• Atrial Fibrillation (complications, drug therapy)
• Brain Ischemia (etiology, prevention & control)
• Female
• Humans
• Ischemic Stroke
• Male
• Secondary Prevention
• Stroke (drug therapy, etiology, prevention & control)