title: A comparative pharmacodynamic study of ticagrelor versus clopidogrel and ticagrelor in patients undergoing primary percutaneous coronary intervention: the CAPITAL RELOAD study.
abstract: BACKGROUND
  In patients undergoing primary percutaneous coronary intervention (PPCI) ticagrelor is superior to clopidogrel in reducing cardiovascular events. This study sought to evaluate the effect of clopidogrel pretreatment on the pharmacodynamics of ticagrelor in patients undergoing PPCI.
  
  
  METHODS
  We measured platelet reactivity using the VerifyNow P2Y12 assay at baseline, 1, 2, 4, 6, 12, 24, and 48 hours following ticagrelor bolus in patients previously loaded with clopidogrel (C+T) and in thienopyridine-naive patients (T) referred to our centre for PPCI.
  
  
  RESULTS
  In total, 52 consecutive eligible patients with ST-elevation myocardial infarction (STEMI) were enrolled (27 C+T and 25 T). Baseline characteristics and mean baseline platelet reactivity units (PRUs) were similar between the groups. The primary endpoint, the proportion of patients achieving a PRU<208 at 2 hours, was more frequently achieved in the C+T group compared to T treatment (76.0% vs 44.4%, p= 0.026). Notably, C+T therapy resulted in fewer patients with high platelet reactivity at 1 hour (56.0% vs. 14.8%), 4 hours (100.0% vs. 61.5%) and 6 hours (100.0% vs. 64%, p<0.01 for all comparisons). Furthermore, C+T therapy was associated with lower PRU values from 2 to 48 hours.
  
  
  CONCLUSIONS
  In patients referred for PPCI, ticagrelor bolus following clopidogrel resulted in more rapid and profound platelet inhibition, demonstrating a positive pharmacodynamic interaction. Further study is needed to determine if this pharmacodynamic effect translates into reduced clinical events.
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hibbert
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Ronnen
authors.initials: R
authors.lastname: Maze
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Pourdjabbar
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Trevor
authors.initials: T
authors.lastname: Simard
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: F Daniel
authors.initials: FD
authors.lastname: Ramirez
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Rohit
authors.initials: R
authors.lastname: Moudgil
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: Blondeau
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Marino
authors.initials: M
authors.lastname: Labinaz
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dick
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Glover
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Froeschl
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Marquis
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Derek Y F
authors.initials: DY
authors.lastname: So
authors.affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Michel R
authors.initials: MR
authors.lastname: Le May
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine