ACC: PHOENIX rises above other CHAMPION trials for cangrelor’s safety, efficacy

SAN FRANCISCO—Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding, based on the late-breaking CHAMPION PHOENIX trial, presented March 10 at the American College of Cardiology (ACC) scientific session. However, some still question its role in clinical practice, if approved by the FDA.

The antiplatelet drug, cangrelor, is a potent intravenous adenosine diphosphate (ADP)–receptor antagonist that acts rapidly and has quickly reversible effects, explained the study’s lead author Deepak L. Bhatt, MD, MPH, chief of cardiology at VA Boston Healthcare System and director of the integrated interventional cardiovascular program at Brigham and Women’s Hospital in Boston.

Previously in CHAMPION PCI and CHAMPION PLATFORM, cangrelor did not demonstrate superiority over clopidogrel in reducing the composite of death, MI or ischemic revascularization 48 hours after PCI, nor did the investigative drug prove superior over placebo for the combined endpoint of MI, all-cause mortality and revascularization. Yet, the drug may have some benefits for stent thrombosis. Those two randomized, controlled trials were at the 2009 American Heart Association scientific sessions.

For this double-blind, placebo-controlled CHAMPION PHOENIX trial, the researchers randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and guideline-recommended therapy to receive a bolus and infusion of cangrelor or a loading dose of 600 mg or 300 mg of clopidogrel.

The primary efficacy endpoint was a composite of death, MI, ischemia-driven revascularization or stent thrombosis at 48 hours after randomization; the key secondary endpoint was stent thrombosis at 48 hours. The primary safety endpoint was severe bleeding at 48 hours.

The rate of the primary efficacy endpoint was 4.7 percent in the cangrelor group and 5.9 percent in the clopidogrel group. The rate of the primary safety endpoint was 0.16 percent in the cangrelor group and 0.11 percent in the clopidogrel group. Stent thrombosis developed in 0.8 percent of the patients in the cangrelor group and in 1.4 percent in the clopidogrel group.

The rates of adverse events related to the study treatment were low in both groups, though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel (1.2 vs. 0.3 percent).

Also, Bhatt pointed out that the benefit was sustained through 30 days, with no excess in severe bleeding or transfusions.

The study was simultaneously published in the New England Journal of Medicine. In the study’s accompanying editorial, Richard A. Lange, MD, and L. David Hillis, MD, from the University of Texas Health Sciences Center in San Antonio, wrote, “Importantly, cangrelor did not cause increased bleeding. These results differ from those of two previous [CHAMPION} trials.”

However, Lange and Hillis also wrote that “the occurrence of ‘definite’ stent thrombosis did not differ significantly between the two treatments. The manner in which stent thrombosis was identified is not described, nor is it clear whether all coronary angiograms were analyzed by a core laboratory to determine whether stent thrombosis occurred.”

Based on the findings, Bhatt concluded that “IV cangrelor may be an attractive option across the full spectrum of PCI patients, including stable angina, non-STEMI and STEMI. I would use this in my practice in this way.”

Yet, Lange and Hillis wrote that “it would seem that although some patients undergoing PCI may benefit from an intravenous ADP-receptor antagonist, such as cangrelor, the routine use of this therapy for all patients undergoing PCI is not yet justified.”

Bhatt stressed that cangrelor would be particularly useful for patients who will require urgent surgery, not emergent surgery, due to the fast-acting quality of the agent. With the other antiplatelet drugs, the half-life can be up to seven days, so the patient may have to wait to undergo surgery. “After the procedure is done, the physicians can immediately switch to clopidogrel or ticagrelor, if preferred,” he said.

The trial was supported by The Medicines Company.