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Bridging Antiplatelet Therapy With Cangrelor in Patients Undergoing Cardiac Surgery: A Randomized Controlled Trial
Study Questions:
What is the effect of cangrelor, an intravenous, reversible P2Y12 platelet inhibitor, for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG) surgery?
Methods:
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.
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 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.
Conclusions:
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.
Perspective:
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
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