BRIDGE: Cangrelor Provides Effective Maintenance of Platelet Inhibition Without Major Bleeding

SAN FRANCISCO, CALIF.—Results of the BRIDGE trial support the hypothesis that P2Y12 inhibition with the rapid acting agent cangrelor is a safe management strategy in patients who require continued platelet inhibition following thienopyridine interruption prior to cardiac surgery.

“When used as a bridging strategy to CABG after thienopyridine discontinuation, cangrelor at 0.75 mcg/kg/min achieves levels of platelet inhibition known to be associated with a low risk for thrombotic events,”

Dominick J. Angiolillo, MD, PhD, of the University of Florida College of Medicine, Jacksonville, Fla., said. He noted that effects of cangrelor (The Medicines Company) were independent of prior thienopyridine dose and time of discontinuation, were consistent with pharmacodynamic effects during IV infusion and were associated with rapid offset after IV discontinuation prior to surgery.

The prospective, randomized, double blind, placebo-controlled, multicenter trial enrolled 210 patients with ACS treated with a coronary stent (BMS or DES) who discontinued thienopyridine therapy (ticlopinide, clopidogrel or prasugrel) and were awaiting CABG. After thienopyridine therapy was stopped, patients were administered cangrelor or placebo for at least 48 hours, which was then discontinued 1 to 6 hours prior to surgery. The objective was to demonstrate that cangrelor would maintain levels of platelet activity <240 P2Y12 reaction units (PRU) throughout the perioperative period, as measured by the VerifyNow P2Y12 test.

A greater proportion of patients treated with intraveneous cangrelor had low levels of platelet activity throughout the treatment period compared with those treated with placebo (PRU <240: 98.8% vs. 19%; OR 353; 95% CI 45.6-2,728; P<.0001).

The primary safety endpoint, excessive CABG-related bleeding, was similar between the cangrelor and placebo groups (11.8% vs. 10.4%; P=.763), with a total of 22 bleeding events, according to Angiolillo. Results showed no difference between the two groups in individual components of bleeding, such as surgical re-exploration, transfusions and reoperation for bleeding. After examining preoperative bleeding using the ACUITY, GUSTO and TIMI definitions, the BRIDGE investigators found no differences in major bleeds, but an increase in minor pre-CABG bleeding with cangrelor.

“Larger patient samples are warranted to [establish] cangrelor as a bridging therapy in patients with ACS or treated with coronary stents who require surgery,” Angiolillo said.

Cangrelor was administered in a step-wise fashion at predetermined doses until platelet inhibition was >60% in 80% of daily samples or a dose of 2 mcg/kg/min was reached.