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Stroke severity in patients with preceding direct oral anticoagulant therapy as compared to vitamin K antagonists

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Abstract

Background

Although direct oral anticoagulants (DOAC) have proven at least equally effective in the prevention of acute ischemic stroke (AIS) in patients with atrial fibrillation as compared to the vitamin K antagonists (VKA), no reliable data on the severity of AIS of DOAC patients as compared to VKA is available.

Methods

Using a prospectively collected cohort of AIS patients, we performed univariate and multivariate (displayed as adjusted Odds Ratios, OR and 95% confidence intervals, 95% CI) analyses regarding the severity of AIS in patients with preceding DOAC (N = 210) versus VKA (N = 173) therapy. Additionally, we provide a sensitivity analysis considering only patients with warranted therapeutic anticoagulation activity.

Findings

In a comprehensive stroke center population, the frequency of AIS under DOAC was multiple times higher than previously reported at around 6% of all AIS and steadily increasing. National Institute of Health Stroke Scale (NIHSS) in VKA patients (median 7, IQR 2–14) was equal to DOAC (median 5, IQR 2–16) on univariate analysis (P = 0.229). According to the multivariable linear logistic regression analysis adjusting for confounders of severe stroke, VKA was not significantly associated with higher NIHSS scores (β − 0.165, 95% CI − 1.874 to 1.545, P = 0.850) as compared to DOAC. Also in the sensitivity analysis considering only patients with warranted therapeutic OAC therapy, VKA was not significantly associated with higher NIHSS scores (β − 1.392, 95% CI − 3.506 to 0.721, P = 0.195) as compared to DOAC. However, VKA as compared to DOAC was significantly associated with lower rates of good functional outcome at three months (0.527, 95% CI 0.300–0.928), but not with increased mortality (aOR 1.825, 95% CI 0.780–4.273).

Interpretation

Ischemic stroke in patients taking DOAC is an important and frequent scenario. Stroke severity in our real world population dataset is equal in patients taking VKA and DOAC, also in the case of warranted anticoagulation therapy. Preceding VKA as compared to DOAC was associated with lower rates of good functional outcome without excess mortality, but a causal relationship cannot be proven by our study design.

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Funding

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Author information

Author notes

  1. Elias Auer and Sebastién Frey contributed equally.

  2. Simon Jung and Thomas Raphael Meinel contributed equally.

Authors and Affiliations

  1. Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 8, 3010, Bern, Switzerland

    Elias Auer, Sebastién Frey, David J. Seiffge, Martina Goeldlin, Marcel Arnold, Urs Fischer, Simon Jung & Thomas Raphael Meinel

  2. Department of Neurology, Institute of Diagnostic and Interventional Neuroradiology, Institute of Diagnostic, Interventional and Pediatric Radiology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland

    Johannes Kaesmacher

  3. Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Arsany Hakim

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  1. Elias Auer
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Corresponding author

Correspondence to Thomas Raphael Meinel.

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Conflicts of interest

Mr. Meinel has received travel grants from Pfizer. Mr. Kaesmacher has received travel grants from Pfizer and Stryker. Dr. Fischer is a consultant for Medtronic, CSL Behring and Stryker, outside the submitted work. Marcel Arnold received speaking fees and honoraria for scientific advisory boards from Covidien and Medtronic, outside the submitted work. All other authors have nothing to disclose.

Ethical standard

This study has been approved by the appropriate ethics committee and performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Auer, E., Frey, S., Kaesmacher, J. et al. Stroke severity in patients with preceding direct oral anticoagulant therapy as compared to vitamin K antagonists. J Neurol 266, 2263–2272 (2019). https://doi.org/10.1007/s00415-019-09412-y

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  • DOI: https://doi.org/10.1007/s00415-019-09412-y

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