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Plasma levels of direct oral anticoagulants in atrial fibrillation patients at the time of embolic stroke: a pilot prospective multicenter study

  • Pharmacodynamics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Background

Patients with atrial fibrillation (AF) who are on long-term direct oral anticoagulants (DOAC) with low anti-Xa or anti-IIa levels may be at higher risk of recurrent stroke. However, no prospective post-marketing study has investigated these DOAC plasma levels at the time of embolic stroke. The aim of this study was to assess the anti-Xa (rivaroxaban, apixaban) and anti-IIa (dabigatran) plasma levels in DOAC-treated AF patients at the time of acute embolic stroke.

Patients and methods

We prospectively identified 43 patients with AF on long-term DOAC who experienced embolic strokes. We compared the DOAC plasma levels of these patients with a control sample of 57 patients who tolerated long-term therapeutic dose DOAC therapy without any adverse event. DOAC levels were assessed with drug-specific anti-Xa chromogenic analysis (rivaroxaban, apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran).

Results

Dabigatran-treated patients with stroke had significantly lower anti-IIa levels when compared with the trough (40.7 ± 36.9 vs. 85.4 ± 57.2 ng/mL, p < 0.05) and peak samples of the controls (40.7 ± 36.9 vs. 138.8 ± 78.7 ng/mL, p < 0.001). Similarly, there were significantly lower anti-Xa levels in apixaban-treated patients with stroke compared to the trough control samples (72.4 ± 46.7 vs. 119.9 ± 81.7 ng/mL, p < 0.05), and in rivaroxaban- and apixaban-treated patients when compared to peak control samples (rivaroxaban: 42.7 ± 31.9 vs. 177.6 ± 38.6 ng/mL, p < 0.001; apixaban: 72.4 ± 46.7 vs. 210.9 ± 88.7 ng/mL, p < 0.001).

Conclusion

This observational study showed significantly lower anti-IIa and anti-Xa plasma levels in AF patients with embolic stroke compared to those who tolerated long-term therapeutic dose DOAC therapy.

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Data availability

All data are available at corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank Mr. Paul McCullough for proofreading and A/Prof. Marián Grendár, PhD. for the assistance with statistical analysis.

Funding

This study was supported by research project APVV (Slovak Research and Development Agency) 16–0020, by research project of Research Agency of Slovak Ministry of Education, Science and Sports (VEGA) 1/0090/20, and by research and development project ITMS2014 + : 313011V344.

Author information

Authors and Affiliations

  1. Department of Neurology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic

    Vladimír Nosáľ, Jana Dluhá, Štefan Sivák, Lucia Babálová & Egon Kurča

  2. Department of Neurology, Faculty of Social Sciences and Health Care, Constantine the Philosopher University in Nitra, Teaching Hospital in Nitra, Nitra, Slovak Republic

    Andrea Petrovičová & Gabriel Hajaš

  3. Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, National Centre of Hemostasis and Thrombosis, Comenius University in Bratislava, Martin, Slovak Republic

    Ingrid Škorňová, Lucia Stančiaková, Ján Staško & Peter Kubisz

  4. Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 03659, Martin, Slovak Republic

    Tomáš Bolek, Matej Samoš & Marián Mokáň

Authors
  1. Vladimír Nosáľ
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  2. Andrea Petrovičová
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  3. Ingrid Škorňová
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  4. Tomáš Bolek
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Contributions

V.N., I.Š., T.B., M.S., J.S., and E.K. designed the study. V.N., A.P., T.B., and M.S. drafted the manuscript. A.P., T.B., J.D., Š.S., L.B., G.H., and M.S. collected, analyzed, and interpreted the clinical data. I.Š. supervised anti-Xa activity assessment; I.Š. and L.S. assessed the anti-Xa activity, analyzed, and interpreted the laboratory data. Š.S., G.H., J.S., P.K., E.K., and M.M. revised the manuscript critically. All the authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Matej Samoš.

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Ethics approval and informed consent

This research was done according to ethical standards and was approved by the local ethical committee (Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava). The patients agreed to participate in the research and signed informed consent for study participation.

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The authors declare no competing interests.

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Nosáľ, V., Petrovičová, A., Škorňová, I. et al. Plasma levels of direct oral anticoagulants in atrial fibrillation patients at the time of embolic stroke: a pilot prospective multicenter study. Eur J Clin Pharmacol 78, 557–564 (2022). https://doi.org/10.1007/s00228-022-03280-8

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  • DOI: https://doi.org/10.1007/s00228-022-03280-8

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