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Early apixaban therapy after ischemic stroke in patients with atrial fibrillation

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Abstract

Background

The optimal timing of anticoagulation after stroke in patients with atrial fibrillation (AF) is unknown. We aimed to objectively assess the rate of radiological hemorrhagic transformation (HT) associated with early anticoagulation.

Patients and methods

A prospective, open label study (NCT04435418) of patients with AF treated with apixaban within 14 days of ischemic stroke/TIA onset was conducted. Baseline and follow-up CT scans were assessed for HT and graded using European Cooperative Acute Stroke Study (ECASS) criteria. The primary endpoint was symptomatic HT. Incident HT rates were assessed as Objective Performance Criteria.

Results

One-hundred AF stroke patients, with a mean age of 79 ± 11 years were enrolled. Median infarct volume was 4 (0.5–10.75) ml. Median time from index event onset to apixaban initiation was 2 (1–6) days, and median baseline NIHSS was 4 (1–9). Asymptomatic HT on baseline imaging was present in 15 patients. Infarct volume (OR = 1.1, [1.02–1.12], p < 0.0001) and NIHSS (OR = 1.11, [1.03–1.20], p = 0.007) were both associated with baseline HT. No patients developed symptomatic HT or systemic hemorrhage. Incident asymptomatic HT was seen on follow-up CT scan in 3 patients. Patients with incident HT were functionally independent (mRS = 0–2) at 90 days. Recurrent ischemic events occurred within 90 days in 13 patients, 4 of which were associated with severe disability (mRS 3–5) and 4 with death.

Discussion

Early apixaban treatment did not precipitate symptomatic HT after stroke. All HT was asymptomatic identified on imaging. Recurrent ischemic events were common and clinically symptomatic.

Conclusions

Symptomatic HT rates are likely to be low in randomized trials of DOAC initiation post-stroke. Recurrent ischemic stroke may be the major clinical outcome. These data may be used as expected event rates when calculating sample size requirements for future safety/efficacy trials of early versus late DOAC initiation after AF-related stroke.

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Acknowledgements

AA thanks King Saud University and the Saudi Arabian Ministry of Education for Residency and Fellowship funding. AA thanks The University of Alberta Hospital Foundation and the Neuroscience and Mental Health Institute for the Neurology Fellowship Award. KSB held a Canada Research Chair in Cerebrovascular Disease and the Heart and Stroke Foundation of Alberta, NWT and Nunavut Professorship in Stroke Medicine and is a currently supported by a New South Wales Health Senior Cardiovascular Scientist award.

Funding

This study was supported in part by Pfizer Canada. Additional support was provided by the Canada Research Chairs Program and the Heart and Stroke Foundation of Alberta, Northwest Territories and Nunavut. The study sponsor was ‘The Governors of the University of Alberta.’ None of the funding organizations had any role in study design, data collection, analysis, interpretation, or manuscript preparation. All authors had full access to all data in the study and had final responsibility for the presentation of results.

Author information

Authors and Affiliations

  1. University of Alberta, Medicine, Edmonton, Canada

    Anas Alrohimi, Brian Buck, Glen Jickling, Ashfaq Shuaib, Sibi Thirunavukkarasu & Ken S. Butcher

  2. King Saud University, Medicine, Riyadh, Saudi Arabia

    Anas Alrohimi

  3. Prince of Wales Clinical School, University of New South Wales, Level 1, South Wing, Edmund Blacket Building, Sydney, Australia

    Ken S. Butcher

  4. Prince of Wales Hospital, Randwick, NSW, 2031, Australia

    Ken S. Butcher

Authors
  1. Anas Alrohimi
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  2. Brian Buck
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  3. Glen Jickling
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  4. Ashfaq Shuaib
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  5. Sibi Thirunavukkarasu
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  6. Ken S. Butcher
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Corresponding author

Correspondence to Ken S. Butcher.

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Conflicts of interest

KB reports grants and personal fees from Boehringer Ingleheim, grants and personal fees from BMS-Pfizer Alliance, grants and personal fees from Bayer, grants and personal fees from Servier Canada, outside the submitted work. AA, BB, GJ, AS, and ST have nothing to disclose.

Ethical approval

The research protocol was approved by our local Human Research Ethics Board.

Informed consent

Written informed consent was obtained from all subjects before the study.

Statement of authorship

Dr. Butcher was the Principal Investigator, responsible for protocol design, funding, and overall conduct of the study, as well as manuscript preparation. Dr. Alrohimi led patient recruitment, performed all image and statistical analyses and wrote the initial draft of the manuscript. Brian Buck, Glen Jickling, Ashfaq Shuaib, and Sibi Thirunavukkarasu recruited patients and made critical revisions of the manuscript.

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Alrohimi, A., Buck, B., Jickling, G. et al. Early apixaban therapy after ischemic stroke in patients with atrial fibrillation. J Neurol 268, 1837–1846 (2021). https://doi.org/10.1007/s00415-020-10335-2

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  • DOI: https://doi.org/10.1007/s00415-020-10335-2

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