Rivaroxaban reduces thromboxane induced platelet aggregation - the forgotten Compass Arm?

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 µg/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.