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CHAMPION PHOENIX: Cangrelor outperforms clopidogrel during PCI
SAN FRANCISCO — Cangrelor, a potent intravenous adenosine diphosphate-receptor antagonist, significantly reduced the rate of ischemic events, including stent thrombosis, during PCI without increasing severe bleeding when compared with clopidogrel, according to a late-breaking trial presented here.
“Intravenous cangrelor may be an attractive option across the full spectrum of PCI, including stable angina, non-STEMI and STEMI,” Deepak L. Bhatt, MD, MPH, trial investigator with the VA Boston Healthcare System, said during a presentation.
Deepak L. Bhatt
Two earlier large phase 3 trials, CHAMPION PCI and CHAMPION PLATFORM, tested cangrelor in PCI, but neither trial met the primary endpoint, according to Bhatt, who is Chief Medical Editor for Cardiology Today’s Intervention.
The double blind, placebo-controlled CHAMPION PHOENIX trial included 11,145 patients who were undergoing either urgent or elective PCI and receiving guideline-recommended therapy. Bhatt and fellow trial researchers randomly assigned patients to bolus and infusion of cangrelor (The Medicines Company), which acts rapidly and has quickly reversible effects, or a loading of 600 mg or 300 mg of clopidogrel (Plavix, Sanofi-Aventis). They defined the primary efficacy endpoint as a composite of death, MI, ischemia-driven revascularization or stent thrombosis 48 hours after randomization.
Compared with clopidogrel, the primary efficacy endpoint was significantly lower in the cangrelor group (4.7% vs. 5.9%; adjusted OR=0.78; P=.005), while the rate of severe bleeding, the study’s primary safety endpoint, was similar (cangrelor, 0.16% vs. clopidogrel, 0.11%; OR=1.5; P=.44). Further analysis revealed that the number needed to treat with cangrelor to prevent one primary endpoint event was 84 (95% CI, 49-285).
Researchers also reported a lower rate of stent thrombosis in the cangrelor group (0.8% vs. 1.4%; OR=0.62; P=.01).
At 30 day follow-up, the benefit in the composite efficacy endpoint in the cangrelor arm was sustained (6% vs. 7%; OR=0.85; P=.01).
Trial limitations of note, Bhatt said, include the potential for the observed benefits of cangrelor to be attenuated with a longer duration of pretreatment and the use of ticagrelor or prasugrel, and a loading dose of 600 mg has become more common than 300 mg, although the results are still significant in the three-quarters of patients who received 600 mg as the loading dose.
Results of the CHAMPION PHOENIX trial were published simultaneously in The New England Journal of Medicine. – by Brian Ellis
For more information:
Bhatt DL. Late-breaking clinical trials II: Interventional. Presented at: American College of Cardiology Scientific Sessions; March 9-11, 2013; San Francisco.
Bhatt DL. N Engl J Med. 2013;doi:10.1056/NEJMoa1300815.
Disclosure: Bhatt reports receiving research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis and The Medicines Company and reports involvement in unfunded research for FlowCo, PLx Pharma and Takeda. The trial was funded by The Medicines Company.
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The CHAMPION PHOENIX trial supports the platelet hypothesis: therapy with the more potent platelet inhibitor strategy in the patient at high risk for thrombosis will result in less thrombotic event occurrence. In CHAMPION PHOENIX the potent thrombogenic stimulus was PCI. Similar observations were made many years ago in the area of PCI with parenteral glycoprotein IIb/IIIa inhibitor therapy. In the ESPRIT trial patients undergoing non-urgent PCI who were treated with eptifibatide, a reversible agent, had less subsequent ischemic events and the benefit was seen early, within 48 hours, most notably in periprocedural MI. The ESPRIT trial was stopped early because of superior efficacy with eptifibatide versus placebo. In the CHAMPION PHOENIX trial use of a reversible parenteral P2Y12 inhibitor, cangrelor, in patients not sufficiently pretreated with clopidogrel was associated with a similar early benefit. Cangrelor produces a much more rapid and potent level of P2Y12 inhibition than clopidogrel and its pharmacodynamic superiority vs. clopidogrel directly translated into a superior antithrombotic effect. We also learned from the TRITON and PLATO trials that more potent P2Y12 blockade with the new oral P2Y12 inhibitors, prasugrel and ticagrelor, also translated into superior antithrombotic effects.
In summary, the clinical response observed in large scale trials has followed the pharmacodynamic effect and this is exactly what happened in the CHAMPION PHOENIX trial. For me, the CHAMPION PHOENIX trial further solidifies the important role that platelet physiology plays in the genesis of thrombotic events early after PCI. It is a very important study and the investigators should be congratulated for their contribution. In the United States many coronary interventions are performed ad hoc in the absence of adequate clopidogrel pretreatment. Cangrelor provides another important option for the interventional cardiologist to achieve immediate, potent and reversible platelet inhibition.
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CHAMPION PHOENIX was a huge trial that involved patients all over the world. Most interesting was that cangrelor did have a huge benefit, especially since they used the 600-mg dose of clopidogrel. Despite using double-dose clopidogrel in 80% of cases, this is still a highly positive trial. MI and stent clotting were significantly reduced.