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Dabigatran and rivaroxaban do not affect AA- and ADP-induced platelet aggregation in patients receiving concomitant platelet inhibitors

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Abstract

Dabigatran and rivaroxaban are novel, vitamin K-independent oral anticoagulants (NOACs) and act via antagonism of the coagulation factor (F) IIa (dabigatran) or FXa (rivaroxaban), respectively. Compared to vitamin-K-antagonists, NOACs have shown non-inferiority of risk and benefit in patients with non valvular atrial fibrillation (AF). In clinical practice there is increasing use of NOACs combined with platelet inhibitors in patients with AF and coronary artery disease. However, whether NOACs affect the function of platelet inhibitors remains incompletely known. This observational study aimed to assess the platelet function in patients receiving dabigatran or rivaroxaban and concomitant platelet inhibitors. A single centre observational study was performed analysing the platelet aggregation of patients treated with dabigatran or rivaroxaban with or without concomitant platelet inhibitors. Measurements before the initiation of NOAC therapy served as the respective control group. Platelet aggregation was measured by multiple electrode aggregometry and was induced with adenosine diphosphate (ADP, 6.5 µM) and arachidonic acid (AA, 0.5 mM), respectively. In order to evaluate whether NOACs interact with platelet inhibition by ASA or the P2Y12-antagonist clopidogrel, 87 patients were grouped according to their concomitant antiplatelet medication. Comparing the ADP- and AA-induced platelet aggregation in patients without concomitant platelet inhibitors (n = 45) no significant differences under therapy with dabigatran (d) or rivaroxaban (r) compared to the control group (c) were observed. In patients taking clopidogrel as a concomitant platelet inhibitor (n = 21), neither dabigatran nor rivaroxaban affected the ADP-induced platelet aggregation (c 20 ± 11, d 21 ± 14, r 18 ± 8 AU*min, p = 0.200). Patients receiving dabigatran or rivaroxaban in combination with ASA (n = 42; 21 ASA only, 21 ASA + clopidogrel) showed no significant differences of the AA-induced aggregation compared to the control group (c 10 ± 8, d 9 ± 7, r 10 ± 8 AU*min, p = 0.810). The antiplatelet effects of ASA and clopidogrel monitored by AA- or ADP-induced platelet aggregation were not affected by NOAC therapy.

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Acknowledgments

This work was supported by a grant from the Deutsche Forschungsgemeinschaft (OL 371/1–1 to Christoph B. Olivier).

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    Authors and Affiliations

    1. Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany

      Christoph B. Olivier, Patrick Weik, Melanie Meyer, Philipp Diehl, Christoph Bode, Martin Moser & Qian Zhou

    2. Center for Medical Biometry and Medical Informatics, Medical Center - University of Freiburg, Freiburg, Germany

      Susanne Weber

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    1. Christoph B. Olivier
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    Correspondence to Christoph B. Olivier.

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    Conflict of interest

    C Olivier, P. Diehl, Q. Zhou and M. Moser are investigators in PIONEER AF-PCI. P. Diehl received speaker’s fees from Lilly Deutschland GmbH. C. Bode received speaker’s fees from Merck, AstraZeneca, Sanofi und Bayer. M. Moser received speaker’s fees from Bayer Vital GmbH, AstraZeneca GmbH, Daiichi Sankyo Deutschland GmbH, Pfizer/Bristol-Myers Squibb, Berlin Chemie AG, Lilly Deutschland GmbH, Boehringer Ingelheim Pharma GmbH & Co. and KG Sanofi-Aventis Deutschland GmbH.

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    Martin Moser and Qian Zhou have contributed equally to this work.

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    Olivier, C.B., Weik, P., Meyer, M. et al. Dabigatran and rivaroxaban do not affect AA- and ADP-induced platelet aggregation in patients receiving concomitant platelet inhibitors. J Thromb Thrombolysis 42, 161–166 (2016). https://doi.org/10.1007/s11239-016-1350-7

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