Platelet Inhibition to Bridge Patients for CABG

The use of cangrelor, an intravenous antagonist of the P2Y12 receptor, to bridge patients after they discontinue antiplatelet therapy in preparation for coronary artery bypass graft (CABG) surgery, was shown to effectively provide platelet inhibition at levels posing a low risk of thrombosis, according to results of a recent study [JAMA. 2012;307(3):265-274]. Patients undergoing procedures such as CABG are advised to discontinue antiplatelet therapy (particularly P2Y12 receptor inhibitors known as thienopyridines) 5 to 7 days before surgery to minimize the risk of bleeding complications, although this increases the risk of thrombosis. Bridging patients to their surgery via a means of platelet inhibition that involves minimal risk of both ischemic events and bleeding complications is ideal to mitigate the risk of thrombosis. Researchers recently conducted a study known as BRIDGE to determine whether cangrelor would be a safe, effective method to bridge patients after they discontinued thienopyridine therapy until CABG was performed. BRIDGE consisted of 2 stages. Stage 1 was an open-label phase conducted between January and August 2009, the goal of which was to identify the proper dose of cangrelor that would achieve the desired antiplatelet effect after thienopyridines were discontinued. Stage 2 was prospective, randomized, double-blind, and placebo-controlled, and took place between October 2009 and April 2011. The goal of stage 2 was to examine whether the dose of cangrelor identified in stage 1 would maintain the correct levels of platelet reactivity throughout the preoperative period. Along with the usual standard of care, patients in this stage also received either cangrelor or placebo, beginning after thienopyridine therapy was stopped and continuing throughout the preoperative period, up to 1 to 6 hours before surgery. Adults scheduled for a planned, not emergency, CABG (no sooner than 48 hours but no longer than 7 days from randomization) were eligible for study inclusion if they were also taking a thienopyridine within at least 72 hours before randomization. Platelet function was assessed using the point-of-care platelet function test and was performed daily during study drug infusion. The primary efficacy end point of the study (stage 1) was maintenance of platelet inhibition in at least 80% of patient samples above 60% as determined by point-of-care platelet function testing; for stage 2, the proportion of patients with platelet reactivity <240 P2Y12 reaction units for all samples assessed during study drug infusion prior to surgery. The primary safety end point was excessive CABG surgery–related bleeding. The researchers used logistic regression to analyze the primary efficacy end point. Results from stage 1, consisting of 10 patients, half of whom were given cangrelor at a dose of 0.5 mcg/kg per minute and the other half 0.75 mcg/kg per minute, showed the 0.75-mcg/kg per minute dose to be correct for maintaining the efficacy end point (94.4%; 95% confidence interval, 83.9%-100%). This became the dose used in stage 2, which consisted of 210 patients randomized to either cangrelor (n=106) or placebo (n=104). Results showed 98.8% of the cangrelor group achieved the primary efficacy end point compared with 19% of the placebo group (P<.001). The primary safety end point occurred in a total of 22 patients but was not significantly different between the 2 groups.