title: Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial.
abstract: BACKGROUND
  Thienopyridines are among the most widely prescribed medications, but their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5 to 7 days prior to surgery to minimize bleeding.
  
  
  OBJECTIVE
  To evaluate the use of cangrelor, an intravenous, reversible P2Y(12) platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG) surgery.
  
  
  METHODS
  Prospective, randomized, double-blind, placebo-controlled, multicenter trial, involving 210 patients with an acute coronary syndrome (ACS) or treated with a coronary stent and receiving a thienopyridine awaiting CABG surgery to receive either cangrelor or placebo after an initial open-label, dose-finding phase (n = 11) conducted between January 2009 and April 2011. Interventions Thienopyridines were stopped and patients were administered cangrelor or placebo for at least 48 hours, which was discontinued 1 to 6 hours before CABG surgery.
  
  
  METHODS
  The primary efficacy end point was platelet reactivity (measured in P2Y(12) reaction units [PRUs]), assessed daily. The main safety end point was excessive CABG surgery-related bleeding.
  
  
  RESULTS
  The dose of cangrelor determined in 10 patients in the open-label stage was 0.75 μg/kg per minute. In the randomized phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary end point, PRU <240; 98.8% (83 of 84) vs 19.0% (16 of 84); relative risk [RR], 5.2 [95% CI, 3.3-8.1] P < .001). Excessive CABG surgery-related bleeding occurred in 11.8% (12 of 102) vs 10.4% (10 of 96) in the cangrelor and placebo groups, respectively (RR, 1.1 [95% CI, 0.5-2.5] P = .763). There were no significant differences in major bleeding prior to CABG surgery, although minor bleeding episodes were numerically higher with cangrelor.
  
  
  CONCLUSIONS
  Among patients who discontinue thienopyridine therapy prior to cardiac surgery, the use of cangrelor compared with placebo resulted in a higher rate of maintenance of platelet inhibition.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00767507.
authors.affiliation: Department of Cardiology, University of Florida, Jacksonville, USA.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Michael S
authors.initials: MS
authors.lastname: Firstenberg
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Price
authors.forename: Pradyumna E
authors.initials: PE
authors.lastname: Tummala
authors.forename: Martin
authors.initials: M
authors.lastname: Hutyra
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Welsby
authors.forename: Michele D
authors.initials: MD
authors.lastname: Voeltz
authors.forename: Harish
authors.initials: H
authors.lastname: Chandna
authors.forename: Chandrashekhar
authors.initials: C
authors.lastname: Ramaiah
authors.forename: Miroslav
authors.initials: M
authors.lastname: Brtko
authors.forename: Louis
authors.initials: L
authors.lastname: Cannon
authors.forename: Cornelius
authors.initials: C
authors.lastname: Dyke
authors.forename: Tiepu
authors.initials: T
authors.lastname: Liu
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Steven V
authors.initials: SV
authors.lastname: Manoukian
authors.forename: Jayne
authors.initials: J
authors.lastname: Prats
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D054058:Acute Coronary Syndrome / Q000601:surgery; D000249:Adenosine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016063:Blood Loss, Surgical; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019106:Postoperative Hemorrhage / Q000139:chemically induced*; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D015607:Stents; D058924:Thienopyridines / Q000008:administration & dosage; D013927:Thrombosis / Q000517:prevention & control
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058924:Thienopyridines; D000249:Adenosine Monophosphate; C117446:cangrelor