• Dominick J Angiolillo, Michael S Firstenberg, Matthew J Price, Pradyumna E Tummala, Martin Hutyra, Ian J Welsby, Michele D Voeltz, Harish Chandna, Chandrashekhar Ramaiah, Miroslav Brtko, Louis Cannon, Cornelius Dyke, Tiepu Liu, Gilles Montalescot, Steven V Manoukian, Jayne Prats, Eric J Topol, and BRIDGE Investigators.
• Department of Cardiology, University of Florida, Jacksonville, USA.
• JAMA. 2012 Jan 18;307(3):265-74.

ContextThienopyridines 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.ObjectiveTo 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 PatientsProspective, 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 MeasuresThe 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.ResultsThe 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.ConclusionsAmong 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 Registrationclinicaltrials.gov Identifier: NCT00767507.

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