title: The direct factor Xa inhibitor Rivaroxaban reduces platelet activation in congestive heart failure.
abstract: BACKGROUND
  Platelet activation in congestive heart failure (CHF) contributes to an increased risk for thromboembolic complications. Rivaroxaban, the first oral direct FXa inhibitor is approved in Europe for prevention and treatment of venous thrombosis, pulmonary embolism, and prevention of thromboembolic events in atrial fibrillation. As heart failure is an important risk factor for thromboembolism and increased platelet activation is common in heart failure, we investigated the potential effect of Rivaroxaban treatment on platelets in an experimental CHF model.
  
  
  RESULTS
  Chronic myocardial infarction was induced in male Wistar rats by coronary ligation. Rats were randomized to placebo or Rivaroxaban (3 and 10mg/kg once daily). After 10 weeks platelet activation was assessed. Platelet-bound fibrinogen, detected by flow-cytometry, was significantly increased in CHF-Placebo (p<0.05) and reduced following treatment with Rivaroxaban (p<0.05 vs. CHF-Placebo). ADP-induced aggregation was significantly enhanced in CHF-Placebo vs. sham-operated animals (p<0.05) and normalized following chronic FXa inhibition (p<0.05 vs. CHF-Placebo). In separate in vitro experiments, attenuated platelet aggregation was present after incubating whole blood directly with Rivaroxaban but absent when the experiment was performed in platelet-rich plasma only. Thus, a direct effect on platelets could be excluded.
  
  
  CONCLUSIONS
  Chronic direct factor Xa inhibition using Rivaroxaban reduces platelet activation in CHF rats by attenuating the secondary phase of ADP-induced platelet aggregation. Thus, Rivaroxaban may constitute a useful approach to prevent thromboembolic complications and reduce platelet activation in CHF at the same time.
authors.affiliation: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Flierl
authors.forename: Daniela
authors.initials: D
authors.lastname: Fraccarollo
authors.forename: Jan
authors.initials: J
authors.lastname: Micka
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäfer
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D065427:Factor Xa Inhibitors; D006333:Heart Failure / Q000097:blood*; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000069552:Rivaroxaban; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban
keywords: BSA; CHF; Congestive heart failure; DMSO; Direct FXa inhibitor; FITC; FX; G-protein coupled receptor; GPCR; LVEDP; MFI; PBS; PLA; PMA; PRP; Platelet activation; Rivaroxaban; TF; WB; bovine serum albumin; congestive heart failure; dimethyl sulfoxide; factor X; fluorescein isothiocyanate; left ventricular end-diastolic pressure; mean fluorescence intensity; phosphate-buffered saline; platelet-rich plasma; platelet–leukocyte aggregates; platelet–monocyte aggregates; tissue factor; whole blood