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Dannenberg, Lisa; M'Pembele, René; Mourikis, Philipp; Helten, Carolin; Zako, Saif; Ahlbrecht, Samantha; Richter, Hannah; Zikeli, Dorothee; Benkhoff, Marcel; Huhn-Wientgen, Ragnar; Thienel, Manuela; Levkau, Bodo; Kelm, Malte; Petzold, Tobias und Polzin, Amin (2021): Rivaroxaban reduces thromboxane induced platelet aggregation - the forgotten Compass Arm? In: Platelets, Bd. 32, Nr. 8: S. 1126-1128

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Abstract

Background: Recent guidelines only recommend 'vascular dose' rivaroxaban in combination with aspirin in chronic coronary syndrome (CCS) patients with high risk of ischemic events However, in the COMPASS trial, a reduction of MACCE appeared for low-dose rivaroxaban alone compared to aspirin as well. It was recently shown that FXa induces platelet aggregation via protease activated receptor 1 (PAR-1) which is in turn attenuated by rivaroxaban. However, a potential impact of rivaroxaban on TX B2 formation is unclear.Methods and Results: TX B2 levels were measured in supernatant from washed platelets after FXa (52 mu g/ml) induced platelet aggregation. TX B2 levels were significantly higher in supernatant from FXa-stimulated platelets compared to unstimulated control (Control 23.53 +/- 14.15 ng/ml vs. FXa stimulated 77.4 +/- 64.14 ng/ml;p = .0025). This effect was abolished in the presence of 100pM rivaroxaban (Control 23.53 +/- 14.15 ng/ml vs. FXa stimulated and rivaroxaban 22.15 +/- 24.74 ng/ml;p = .5142). Next, we investigated the effects of 100pM rivaroxaban on platelet aggregation induced by U46619 (TX receptor agonist) using light transmission aggregometry. Platelet aggregation quantified by maximum of aggregation (MoA%) was significantly lower in presence of rivaroxaban (U46619 40.18 +/- 20.51% vs. U46619+ rivaroxaban 19.26 +/- 15.46%;p = .0274).Conclusion: Our results indicate direct effects of rivaroxaban on the cyclooxygenase-1- TX axis during platelet aggregation. Hence, it seems reasonable that the 'forgotten compass arm' (rivaroxaban alone) might be an alternative to the rivaroxaban plus aspirin combination in CCS patients.

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