Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial

JAMA. 2012 Jan 18;307(3):265-74. doi: 10.1001/jama.2011.2002.


Context: 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.

Design, setting, and patients: 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.

Main outcome measures: 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.

Trial registration: Identifier: NCT00767507.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / surgery
  • Adenosine Monophosphate / adverse effects
  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Loss, Surgical*
  • Coronary Artery Bypass*
  • Coronary Artery Disease / surgery
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Postoperative Hemorrhage / chemically induced*
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Stents
  • Thienopyridines / administration & dosage
  • Thrombosis / prevention & control


  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Thienopyridines
  • Adenosine Monophosphate
  • cangrelor

Associated data