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

Oliver Borst, Patrick Munzer, Nada Alnaggar, Sascha Geue, Roland Tegtmeyer, Dominik Rath, Michal Droppa, Peter Seizer, Stefan Heitmeier, Johan W. M. Heemskerk, Lisa K. Jennings, Robert F. Storey, Dominick J. Angiolillo, Bianca Rocca, Henri Spronk, Hugo Ten Cate, Meinrad Gawaz, Tobias Geisler*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Web of Science)

Abstract

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 the anticoagulatory effects of VLD FXa inhibition on top of guideline-adherent dual-antiplatelet therapy (DAPT) in patients with ACS. Patients with non-ST-elevation myocardial infarction (NSTEMI) receiving oral DAPT (ASA + clopidogrel, n = 20; or ASA + ticagrelor, n = 20) were prospectively enrolled in a nonrandomized study. Coagulation-and 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 significantly decreased coagulation-dependent (AR-chip) thrombus formation in patients treated with ASA plus P2Y(12) inhibitor (clopidogrel/ticagrelor), whereas the pure platelet-dependent (PL-chip) thrombus formation was not affected at all. Adjunctive rivaroxaban therapy was not associated with significant differences in platelet aggregation assessed by light-transmission aggregometry (LTA). Nevertheless, according to fluorescence-activated cell sorter analysis, VLD rivaroxaban treatment resulted in a significantly reduced expression of platelet HMGB-1, whereas P-selectin exposure was not affected. Furthermore, an enhanced effect of rivaroxaban on total thrombus formation and TG was observed in particular in clopidogrel nonresponder patients defined as adenosine 5'-diphosphate-induced LTA >= 40%. VLD rivaroxaban reduces thrombus formation and platelet-dependent TG in patients with ACS receiving DAPT, which can be of potential ischemic benefit.
Original languageEnglish
Pages (from-to)715-730
Number of pages16
JournalBlood advances
Volume2
Issue number6
DOIs
Publication statusPublished - 27 Mar 2018

Keywords

  • ACUTE CORONARY SYNDROME
  • ANTIPLATELET THERAPY
  • THROMBIN GENERATION
  • PLATELET REACTIVITY
  • ATRIAL-FIBRILLATION
  • ARTERY-DISEASE
  • ACTIVATION
  • TRIAL
  • HMGB1
  • RECRUITMENT

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