Cangrelor maintained platelet inhibition without major bleeding for patients who require CABG

Issue: December 2011

TCT 2011

SAN FRANCISCO — The intravenous use of the investigational drug cangrelor was effective in maintaining platelet inhibition in patients on thienopyridines who required CABG, according to the BRIDGE clinical trial investigators.

Dominick J. Angiolillo, MD, PhD, presented the primary BRIDGE results at the 2011 Transcatheter Cardiovascular Therapeutics scientific symposium. Results showed that more patients treated with cangrelor (The Medicines Company) had low levels of platelet reactivity, as measured in P2Y12 reaction units (PRU) — the primary efficacy endpoint — during the entire treatment period vs. patients treated with placebo (PRU <240: 98.8% vs. 19%; OR=353; 95% CI, 45.6-2,728).

The main safety endpoint of excessive CABG-related bleeding occurred in 11.8% of cangrelor-treated patients vs. 10.4% of placebo-treated patients (P=.76). The BRIDGE investigators reported no significant differences in major bleeding before CABG; however, minor bleeding was numerically higher with cangrelor.

The goal of the BRIDGE trial was to determine whether cangrelor could be used as a “bridge” between discontinuing thienopyridines and surgery, according to the researchers. The prospective, randomized, double blind, placebo-controlled, multicenter trial included 210 patients with acute coronary syndrome or treated with a coronary stent on a thienopyridine awaiting CABG. Patients were randomly assigned to cangrelor or placebo after an initial open-label, dose-finding phase. After thienopyridines were stopped, patients were administered cangrelor or placebo for at least 48 hours, which was then discontinued 1 to 6 hours before 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,” said Angiolillo, of the University of Florida College of Medicine, Jacksonville, Fla. “Larger patient samples are warranted to more definitively assert the safety and efficacy of cangrelor as a bridging therapy in patients with ACS or treated with coronary stents who require surgery.” – by Katie Kalvaitis

Disclosure: Dr. Angiolillo has received honoraria for lectures from Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly and Sanofi-Aventis; honoraria for consulting/advisory board from Abbott Vascular, Accumetrics, Arena Pharmaceuticals, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Evola, Medicure, Novartis, Portola Pharmaceuticals, Sanofi-Aventis and The Medicines Company; and research grants from Accumetrics, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Otsuka, Portola Pharmaceuticals, Sanofi-Aventis, Schering-Plough and The Medicines Company.

For more information:

Angiolillo DJ. Plenary session V. Late-breaking clinical trials and first report investigations I. Presented at: the 2011 Transcatheter Cardiovascular Therapeutics Scientific Symposium; Nov. 7-11; San Francisco.

PRU is [increasingly] being used as a surrogate marker for prevention of clinical events such as stent thrombosis. Therefore, the results need to be toned down a little because there is no guarantee that a PRU of ,240 is associated with no stent thrombosis. It would take a study of more than 1,000 patients to be able to detect a real benefit in preventing stent thrombosis. On the other side of the coin, what happens after you suddenly withdraw patients from IV cangrelor? Is there a rebound? Since all of these patients are having cardiac surgery and being revascularized, we won't know. Therefore, we should be very careful not to extrapolate the results of BRIDGE to other groups of patients needing to interrupt their dual anti-platelet therapy for non cardiac surgery.

– Marc Cohen, MD
Cardiology Today Editorial Board member

Disclosure: Dr. Cohen speaks for and has received honoraria from Bristol-Myers Squibb, Merck and Sanofi-Aventis. He has participated on advisory boards for AstraZeneca and Janssen.

Follow CardiologyToday.com on Twitter.