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Comparative risks of bleeding, ischemic stroke and mortality with direct oral anticoagulants versus phenprocoumon in patients with atrial fibrillation

  • Pharmacoepidemiology and Prescription
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Abstract

Purpose

The pivotal trials for stroke prevention in non-valvular atrial fibrillation (NVAF) compared rivaroxaban, dabigatran, and apixaban with warfarin, as did most claims-based studies. Comparisons with phenprocoumon, the most frequently used vitamin K antagonist (VKA) in Germany, are scarce.

Methods

Risk of bleeding, ischemic stroke, and all-cause mortality in patients with NVAF were analyzed using data for 2010 to 2014 from a large German claims database. New users of oral anticoagulants from January 2012 to December 2013 were included and observed over 1 year. Baseline characteristics were adjusted using propensity score matching and logistic regression. Several sensitivity analyses were carried out.

Results

Fifty-nine thousand four hundred forty-nine rivaroxaban, 23,654 dabigatran, 4894 apixaban, and 87,997 matched phenprocoumon users were included. Adjusted hazard ratios (95% confidence intervals) compared with phenprocoumon were as follows: hospitalized bleedings: rivaroxaban 1.04 (0.97; 1.11), dabigatran 0.87 (0.77; 0.98), and apixaban 0.65 (0.50; 0.86); ischemic stroke: rivaroxaban 1.05 (0.94; 1.17), dabigatran 1.14 (0.96; 1.35), and apixaban 1.84 (1.20; 2.84); all-cause mortality: rivaroxaban 1.17 (1.11; 1.22), dabigatran 1.04 (0.95; 1.13), and apixaban 1.14 (0.97; 1.34).

Conclusions

With rivaroxaban, no significant differences were observed compared to phenprocoumon with regard to hospitalized bleedings or ischemic strokes. Dabigatran was associated with fewer bleedings and a similar risk of ischemic strokes compared to phenprocoumon. Apixaban was also associated with fewer bleedings but was unexpectedly associated with more ischemic strokes, possibly reflecting selective prescribing. The association of rivaroxaban with higher all-cause mortality unrelated to bleedings or strokes has been described previously but remains to be explained.

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Acknowledgments

The authors would like to thank PD Dr. Michael von Brevern, Prof. Andreas Creutzig, Prof. Thomas Lempert, Prof. Wilhelm Niebling, and Dr. Birke Schneider for their advice on the study design and Prof. Oliver Kuss, University of Düsseldorf, for his helpful comments on propensity score matching, and Siobhan O’Leary for editing assistance.

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Author notes

  1. Mariam Ujeyl and Ingrid Köster contributed equally to this work.

Authors and Affiliations

  1. Drug Commission of the German Medical Association, Herbert-Lewin-Platz 1, 10623, Berlin, Germany

    Mariam Ujeyl, Hans Wille, Thomas Stammschulte & Ursula Gundert-Remy

  2. Department of Psychiatry and Psychotherapy at St. Hedwig Hospital, Charité – Universitätsmedizin Berlin, Berlin, Germany

    Mariam Ujeyl

  3. PMV forschungsgruppe an der Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie, Universität zu Köln, Köln, Germany

    Ingrid Köster, Rebecca Hein, Peter Ihle & Ingrid Schubert

  4. Institut für Medizinische Statistik und Bioinformatik, Universität zu Köln, Köln, Germany

    Rebecca Hein

  5. Institut für Klinische Pharmakologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany

    Sebastian Harder

  6. AOK Bundesverband, Berlin, Germany

    Julian Bleek & Gerhard Schillinger

  7. Wissenschaftliches Institut der AOK – WIdO, Berlin, Germany

    Helmut Schröder & Anette Zawinell

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  1. Mariam Ujeyl
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Corresponding author

Correspondence to Mariam Ujeyl.

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Conflict of interest

The study was supported by a grant to PMV forschungsgruppe by AOK Bundesverband for data analysis. J. Bleek and G. Schillinger are employed by the AOK Bundesverband; H. Schröder and A. Zawinell by the WIdO. PMV forschungsgruppe has received unrestricted grants—not related to the topic of DOAC—from health insurance funds (AOK Bundesverband, AOK Hessen, AOK Baden-Württemberg, BARMER), industry (Sanofi, Ferring), and public funding. The other authors declare no conflict of interest.

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Ujeyl, M., Köster, I., Wille, H. et al. Comparative risks of bleeding, ischemic stroke and mortality with direct oral anticoagulants versus phenprocoumon in patients with atrial fibrillation. Eur J Clin Pharmacol 74, 1317–1325 (2018). https://doi.org/10.1007/s00228-018-2504-7

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  • DOI: https://doi.org/10.1007/s00228-018-2504-7

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