P4403Inhibitory mechanisms of very low dose rivaroxaban in non-ST-elevation myocardial infarction

Abstract

Aims: Very low dose (VLD) factor Xa (FXa) inhibition in combination with acetylsalicylic acid (ASA) and clopidogrel is associated with improved outcomes in patients with acute coronary syndrome (ACS) with a tolerable bleeding risk profile. To date there are no data documenting platelet inhibition and anticoagulatory effects of VLD FXa inhibition on top of guideline adherent dual antiplatelet therapy in ACS patients. Methods and results: Non-ST-elevation myocardial infarction (NSTEMI) patients on oral dual antiplatelet therapy (ASA plus clopidogrel, n=20 or ASA plus ticagrelor, n=20) were prospectively enrolled in a non-randomized study. Coagulationand platelet-dependent thrombin generation (TG), measured by means of the calibrated automated thrombogram, were significantly decreased after in vitro and in vivo addition of rivaroxaban. As shown by a total thrombus-formation analysis approach, rivaroxaban treatment led to a significant decreased coagulationdependent (AR-chip) thrombus formation in patients treated with ASA plus P2Y12 inhibitor (clopidogrel/ticagrelor) while the pure platelet-dependent (PLchip) thrombus formation was not affected at all. Adjunctive rivaroxaban therapy was not associated with significant differences in platelet aggregation (PA) assessed by light-transmission aggregometry (LTA). Nevertheless, according to FACS analysis, VLD rivaroxaban treatment resulted in a significant reduced expression of platelet HMGB-1, while P-selectin exposure was not affected. Furthermore, an enhanced effect of rivaroxaban on total thrombus formation and TG was observed in particular in clopidogrel non-responder patients defined as ADPinduced LTA>40%. Conclusion: VLD rivaroxaban reduces platelet dependent thrombus formation and TG in ACS patients on dual antiplatelet therapy which can be of potential ischemic benefit.