title: Dabigatran and rivaroxaban do not affect AA- and ADP-induced platelet aggregation in patients receiving concomitant platelet inhibitors.
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.
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany. Christoph.Olivier@universitaets-herzzentrum.de.
authors.forename: Christoph B
authors.identifier: http://orcid.org/0000-0002-3065-625X
authors.initials: CB
authors.lastname: Olivier
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Weik
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Meyer
authors.affiliation: Center for Medical Biometry and Medical Informatics, Medical Center - University of Freiburg, Freiburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Weber
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Diehl
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Moser
authors.affiliation: Cardiology and Angiology I, Heart Center, Freiburg University, Hugstetter Str. 55, 79106, Freiburg - Bad Krozingen, Germany.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000991:Antithrombins / Q000494:pharmacology / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000378:metabolism; D000077144:Clopidogrel; D000069604:Dabigatran / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D000069552:Rivaroxaban / Q000494:pharmacology* / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives
chemical_list: D000991:Antithrombins; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D000069552:Rivaroxaban; D000077144:Clopidogrel; D000069604:Dabigatran; D013988:Ticlopidine
keywords: ASA; Clopidogrel; Dabigatran; Rivaroxaban