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Comparative risk of major bleeding with new oral anticoagulants (NOACs) and phenprocoumon in patients with atrial fibrillation: a post-marketing surveillance study

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Abstract

Background

Non-vitamin K antagonist oral anticoagulants (NOACs) are at least as effective and safe as vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF). All pivotal trials have compared NOACs to warfarin. However, other VKAs are commonly used, for instance phenprocoumon.

Patients and methods

A retrospective cohort study using a German claims database assessed the comparative risks of bleeding leading to hospitalization during therapy with NOACs and phenprocoumon in AF patients. Endpoints consisted of major bleeding, gastrointestinal bleeding, and any bleeding. Data were collected from January 1, 2013 to March 31, 2015. Patients newly initiated on dabigatran, apixaban, rivaroxaban, or phenprocoumon were included. Hazard Ratios for bleeding events were derived from Cox proportional hazard models, adjusting for differences in baseline characteristics. Propensity score matching was performed as a sensitivity analysis.

Results

A total of 35,013 patients were identified, including 3138 on dabigatran, 3633 on apixaban, 12,063 on rivaroxaban, and 16,179 on phenprocoumon. Patients prescribed apixaban or phenprocoumon were older compared to those on dabigatran or rivaroxaban and had a higher CHA2DS2-VASc score. After adjusting for baseline confounders, apixaban was associated with lower risks of major bleeding (HR 0.68, 95% CI 0.51–0.90, p = 0.008), gastrointestinal bleeding (HR 0.53, 95% CI 0.39–0.72, p < 0.001), and any bleeding (HR 0.80, 95% CI 0.70–0.92, p = 0.002) compared to phenprocoumon. There were no significant differences in bleeding risk between dabigatran and phenprocoumon. Rivaroxaban was associated with more gastrointestinal bleeding (HR 1.39, 95% CI 1.21–1.60, p < 0.001) and any bleeding (HR 1.19, 95% CI 1.10–1.28, p < 0.001). Sensitivity analysis using propensity score matching confirmed these observations.

Conclusions

Apixaban therapy is associated with a significantly reduced risk of bleeding compared to phenprocoumon. Bleeding risk with dabigatran was similar to that of phenprocoumon but bleeding risk with rivaroxaban was higher.

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Acknowledgements

This analysis was funded by Bristol-Myers Squibb and Pfizer. Part of this work has been presented at the European Society of Cardiology Congress 2016.

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Authors and Affiliations

  1. Division Clinical Electrophysiology, Department of Cardiology, Johann Wolfgang Goethe University, Frankfurt, Germany

    Stefan H. Hohnloser

  2. Pfizer Deutschland GmbH, Berlin, Germany

    Edin Basic

  3. Department of Cardiology, Ludwig Maximilians University, Munich, Germany

    Michael Nabauer

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  1. Stefan H. Hohnloser
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  2. Edin Basic
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Correspondence to Stefan H. Hohnloser.

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Conflict of interest

Professor Hohnloser has served as a consultant for Bayer, BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Jansen. Professor Nabauer has received lecture fees from Bayer, BMS/Pfizer, Boehringer Ingelheim, and Daiichi Sankyo. Dr. Basic is an employee of Pfizer Deutschland GmbH. The authors have indicated that they have no other conflicts of interest regarding the content of this article.

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Hohnloser, S.H., Basic, E. & Nabauer, M. Comparative risk of major bleeding with new oral anticoagulants (NOACs) and phenprocoumon in patients with atrial fibrillation: a post-marketing surveillance study. Clin Res Cardiol 106, 618–628 (2017). https://doi.org/10.1007/s00392-017-1098-x

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  • DOI: https://doi.org/10.1007/s00392-017-1098-x

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