Cangrelor Consistently Comes Out Ahead of Clopidogrel in All PCI Patients

SAN FRANCISCO, CA—The intravenous ADP-receptor inhibitor cangrelor substantially reduces ischemic events across the entire spectrum of patients who need percutaneous coronary intervention (PCI), according to results presented on March 10, 2013, at the American College of Cardiology Scientific Session/i2 Summit. The study, simultaneously published in the New England Journal of Medicine, showed a consistent benefit of the drug in all major subgroups.

For CHAMPION PHOENIX, Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital (Boston, MA), and colleagues randomly assigned 10,942 patients who were undergoing either urgent or elective PCI and were receiving guideline-recommended therapy to receive either a bolus and infusion of cangrelor (The Medicines Company, Parsippany, NJ, n = 5,472) or to receive a loading dose of 600 mg or 300 mg of clopidogrel (n = 5,470). Patients were treated at 153 institutions from September 30, 2010 to October 3, 2012. 

All Signs Point to Cangrelor 

The rates of both the primary composite efficacy endpoint (all-cause death, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours) and the secondary efficacy endpoint (stent thrombosis at 48 hours) were lower in the cangrelor group compared with the clopidogrel group, as was MI (table 1). These results were maintained at 30 days and were consistent across multiple prespecified subgroups.

Table 1. Efficacy Endpoints at 48 Hours

 

 

Cangrelor
(n = 5,472)

Clopidogrel
(n = 5,470)

OR (95% CI)

P Value

Death, MI, Ischemia-driven Revascularization, Stent Thrombosis

4.7%

5.9%

0.78 (0.66-0.93)

0.005

Stent Thrombosis

0.8%

1.4%

0.62 (0.43-0.90)

0.01

MI

3.8%

4.7%

0.80 (0.67-0.97)

0.02

Ischemia-driven Revascularization

0.5%

0.7%

0.74 (0.45-1.20)

0.22

Death

0.3%

0.3%

1.00 (0.52-1.92)

> 0.999


 

The rate of intraprocedural stent thrombosis was also lower in patients treated with cangrelor vs. clopidogrel (0.6% vs. 1.0%; OR 0.65; 95% CI 0.42-0.99; P = 0.04), as was the use of rescue therapy with a glycoprotein IIb/IIIa inhibitor (2.3% vs. 3.5%; OR 0.65; 95% CI 0.52-0.82; P < 0.001) and the rate of procedural complications (3.4% vs. 4.5%; OR 0.74; 95% CI 0.61-0.90; P = 0.002). 

The rate of GUSTO severe bleeding (primary safety endpoint) was slightly higher in the cangrelor group compared with the clopidogrel group (0.16% vs. 0.11%), but the difference was not significant (OR 1.50; 95% CI 0.53-4.22; P = 0.44). When the primary efficacy and safety endpoints were combined, cangrelor treatment still came out ahead of clopidogrel (4.8% vs. 6.0%; OR 0.80; 95% CI 0.68-0.94; P = 0.008).

Both the cangrelor and clopidogrel groups saw similar rates of treatment-related adverse events (20.2% vs. 19.1%; P = 0.13), yet there were more cases of transient dyspnea with cangrelor than clopidogrel (1.2% vs. 0.3%; P < 0.001).

Stirring Up Buzz

Session co-moderator Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY) was impressed with the results. “This is truly a blockbuster randomized trial that will affect practice on numerous levels,” he said. “From a scientific point of view, it’s very exciting because for the first time it establishes and proves the preloading hypothesis with a potent ADP antagonist in patients undergoing PCI, and that’s in all patients.”

Although the study was designed to test superiority, Dr. Bhatt explained, “it was also a trial of strategy [with] a fast onset, fast offset reversible intravenous agent.”

If cangrelor is approved, he would use it “across the full spectrum of PCI” cases, Dr. Bhatt said. “Giving clopidogrel before the coronary anatomy is delineated may be problematic because a certain proportion of the patients will go on to urgent surgery. . . . Therefore having an intravenous agent available provides flexibility to interventionalists to use it during the procedure and afterward [you can] go ahead and use clopidogrel or ticagrelor if that’s what you like.”

CHAMPION PHOENIX is an “incredibly important study for the treatment of patients undergoing PCI, especially those that need to go on to surgery,” panelist Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), said. In addressing intraprocedural stent thrombosis, the study brought to light issues that “we’ve never thought about before,” she added. 

“This is a study of preloading versus essentially no preloading during PCI,” panelist Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), said. “So that might explain the intraprocedural stent thrombosis, which actually [seems to drive] the stent thrombosis adjudication in this case.”

Cangrelor seems to be a “great drug” in STEMI patients because “the agents we give upstream are not going to be taking effect at the time we do the PCI,” Dr. Kirtane added. “In unstable angina NSTEMI, if you are going to get to the lab fast, this would seem to be great. If it’s going to be a while, then to withhold pretreating with another agent might be a situation where we worry a little bit.”

Study Details 

The average age of patients was 64 years and 28% were women. Slightly more than half (56.1%) of patients presented with stable angina, while about a quarter (25.7%) presented with NSTE ACS and 18.2% presented with STEMI. The overall median time from hospital admission to PCI was 4.4 hours.

Note: Drs. Stone, Mehran, and Kirtane are faculty members of the Cardiovascular Research Foundation (CRF), which owns and operates TCTMD. In addition, Dr. Stone and CRF faculty member Philippe Généreux are coauthors of the study.

 

 


 

Source:Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;Epub ahead of print.

 

 

 

 

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Disclosures
  • CHAMPION PHOENIX was sponsored by The Medicines Company.
  • Dr. Bhatt reports receiving research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company.

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