title: Pharmacodynamic effects of cangrelor on platelet P2Y12 receptor-mediated signaling in prasugrel-treated patients.
abstract: OBJECTIVE
  The purpose of this study was to assess the in vitro P2Y12 receptor inhibitory effects of cangrelor on platelets from patients on maintenance prasugrel therapy treated with 2 reloading dose regimens.
  
  
  BACKGROUND
  Despite its more potent and rapid antiplatelet effects compared with clopidogrel, recent studies have shown variability in prasugrel-mediated P2Y12 receptor inhibition, particularly in high-risk settings. Cangrelor is a potent intravenous P2Y12 receptor inhibitor.
  
  
  METHODS
  A total of 60 patients with coronary artery disease on maintenance prasugrel (10 mg/day) therapy were randomized to a 30- or 60-mg reload of prasugrel. The platelet reactivity index (PRI), as assessed by whole-blood vasodilator-stimulated phosphoprotein, was measured with and without in vitro incubation of cangrelor (500 nM) at baseline, and at 1 and 4 h after reload.
  
  
  RESULTS
  In the absence of cangrelor, prasugrel reloading reduced PRI (p < 0.001 for both doses), although a 60-mg reload had greater platelet inhibition compared with a 30-mg reload at 4 h (p = 0.001). Cangrelor was associated with a reduction in PRI values during the overall study time course in patients reloaded with 30 mg (p = 0.001) and 60 mg (p < 0.001) of prasugrel. In patients reloaded with 30 mg prasugrel, cangrelor decreased PRI at each time point (baseline, p < 0.001; 1 h, p = 0.013; 4 h, p = 0.001). In patients reloaded with 60 mg prasugrel, cangrelor decreased PRI at baseline (p < 0.001) and 1 h (p = 0.002); levels of platelet reactivity comparable to those achieved with cangrelor were observed only at 4 h (p = 0.325). The intergroup comparisons with cangrelor were not significant at any time point.
  
  
  CONCLUSIONS
  In patients on maintenance prasugrel therapy exposed to a reloading dose (30 or 60 mg) of prasugrel, in vitro cangrelor is associated with further platelet P2Y12 receptor inhibitory effects.
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rollini
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Francesco
authors.initials: F
authors.lastname: Franchi
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Antonio
authors.initials: A
authors.lastname: Tello-Montoliu
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Ronakkumar
authors.initials: R
authors.lastname: Patel
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Andrew
authors.initials: A
authors.lastname: Darlington
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Ferreiro
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Jung Rae
authors.initials: JR
authors.lastname: Cho
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Ana
authors.initials: A
authors.lastname: Muñiz-Lozano
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Bhaloo
authors.initials: B
authors.lastname: Desai
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Zenni
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Guzman
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida.
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, Florida. Electronic address: dominick.angiolillo@jax.ufl.edu.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005431:Florida; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D010879:Piperazines / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage*; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013876:Thiophenes / Q000008:administration & dosage*; D013997:Time Factors; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes; D000098662:Vasodilator-Stimulated Phosphoprotein; D000249:Adenosine Monophosphate; C117446:cangrelor; D000068799:Prasugrel Hydrochloride
keywords: cangrelor; platelet reactivity; prasugrel