Bridging Antiplatelet Therapy With Cangrelor in Patients Undergoing Cardiac Surgery: A Randomized Controlled Trial
What is the effect of cangrelor, an intravenous, reversible P2Y12 platelet inhibitor, for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG) surgery?
BRIDGE (Maintenance of Platelet Inhibition With Cangrelor After Discontinuation of Thienopyridines in Patients Undergoing Surgery) was a prospective, randomized, double-blind, placebo-controlled, multicenter trial, involving 210 patients with an acute coronary syndrome 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. Thienopyridines were stopped and patients were administered cangrelor or placebo for at least 48 hours, which was discontinued 1-6 hours before CABG surgery. The primary efficacy endpoint was platelet reactivity (measured in P2Y12 reaction units [PRUs]), assessed daily. The main safety endpoint was excessive CABG surgery–related bleeding. The primary efficacy endpoint, the percentage of patients who maintained a PRU <240 during study drug infusion prior to surgery, was analyzed using logistic regression adjusted for the expected days to surgery (either ≤3 days or >3 days) with the intention-to-treat population.
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 endpoint, 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 < 0.001). Excessive CABG surgery–related bleeding occurred in 11.8% (12 of 102) versus 10.4% (10 of 96) in the cangrelor and placebo groups, respectively (RR, 1.1 [95% CI, 0.5-2.5] p = 0.763). There were no significant differences in major bleeding prior to CABG surgery, although minor bleeding episodes were numerically higher with cangrelor.
The authors concluded that 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.
This study suggests that cangrelor infusion consistently achieved and maintained platelet inhibition at levels known to be associated with a low risk of thrombotic events compared with placebo. Furthermore, bridging with a prolonged infusion of cangrelor did not increase major bleeding prior to surgery, although minor bleeding was numerically higher. These data appear to support the hypothesis that intravenous cangrelor is a feasible management strategy in patients waiting for cardiac surgery who require prolonged platelet P2Y12 inhibition after thienopyridine discontinuation.
Keywords: Risk, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Cardiovascular Diseases, Pyridines, Blood Platelets, Coronary Artery Bypass, Cardiac Surgical Procedures, Hemorrhage, Stents, Thienopyridines
< Back to Listings