A new, reversible antiplatelet drug did not demonstrate superiority over a current irreversible one in reducing the composite of death, heart attack or ischemia-related revascularization in the 48 hours after angioplasty, researchers reported in a late-breaking clinical trial presentation at the American Heart Association's Scientific Sessions 2009.
The primary endpoint for CHAMPION PCI was not met, but study researchers say they did find some potential benefit of the new drug, cangrelor, that warrants further investigation.
"Our findings combined with those from a companion trial (CHAMPION PLATFORM) suggest that cangrelor reduces the risk of some clinically meaningful ischemic events in patients undergoing percutaneous coronary intervention (PCI)," said Robert A. Harrington, M.D., principal investigator of the study and professor of medicine at Duke University and director of the Duke Clinical Research Institute in Durham NC. "That includes a possible reduction in Q wave infarction and stent thrombosis."
In CHAMPION PCI -- a phase III, multi-national (200 sites, 18 countries), randomized, double-blind, placebo-controlled trial-- researchers tested the hypothesis that cangrelor provides superior or at least non-inferior performance compared to a 600 milligram (mg) dose of clopidogrel during the 48 hours after PCI.
Investigators planned to enroll about 9,000 patients, but the trial was stopped early (May 2009) with 8,820 patients enrolled after an interim review panel concluded it was unlikely to meet its primary endpoint.
Patients were randomly assigned to receive cangrelor or clopidogrel, the FDA-approved antiplatelet drug that binds irreversibly to platelets.
Those in the cangrelor group got 30 micrograms (mcg) of cangrelor per kilogram (kg) of body weight intravenously, followed by a 4 mcg/kg/per minute infusion for at least two hours. At the end of the procedure, they received a 600 milligram (mg) dose of clopidogrel.
Patients in the clopidogrel group received a standard 600 mg loading dose immediately prior to their PCI. Following the procedure all patients received a maintenance dose of 75 mg of clopidogrel and aspirin therapy (75 mg to 325 mg/day) for at least 30 days thereafter.
Patients received all other anti-clotting therapies according to care standards at their treatment site.
"There was no statistically significant difference in the primary composite endpoint (death, heart attack and ischemic revascularization at 48 hours), which affected 7.5 percent of the cangrelor group vs. 7.1 percent for the clopidogrel group," Harrington said. But, in formal non-inferiority 1160 testing, cangrelor appeared to maintain more than 60 percent of the benefit of 600 (mg) clopidogrel over placebo.
When looked at together with data from the companion trial, researchers also found a reduction in acute stent thrombosis, which are blood clots within the metal mesh stent implanted during PCI to help hold the vessel open. The two treatment groups were well balanced in baseline characteristics. It was noted that there was more minor bleeding associated with cangrelor.
This is the first study to use a 600-mg dose (instead of 300-mg dose) of clopidogrel as the comparison drug and to compare that dose to cangrelor. Cangrelor is the first drug in a class of intravenous P2Y12 receptor antagonists. It provides immediate and intense inhibition of platelet clotting, but, as opposed to clopidogrel, this effect can be reversed.
"With its fast onset and reversibility, cangrelor holds the potential to provide interventional cardiologists with a very rapidly acting platelet inhibitor during PCI. Although the results of the two trials are disappointing in that they failed to meet the primary endpoint, there is enough suggestion in these data of potential benefit that it warrants further investigation," Harrington said.
The companion CHAMPION PLATFORM trial, which had a different patient group and slightly different hypothesis, was presented at the same session.
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