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Novel Antiplatelet a Bridge Between Thienopyridine and CABG
Major Finding: In patients preparing for CABG surgery, 99% of those treated with cangrelor, compared with 19% given placebo, showed adequate...
The investigational antiplatelet drug cangrelor outperformed clopidogrel during percutaneous coronary intervention, significantly reducing the risk of death, myocardial infarction, ischemic events, and stent thrombosis by 22%.
A 20% decrease in heart attack risk accounted for most of the benefit, which was achieved without an increased risk for bleeding. Cangrelor showed some treatment flexibility as well, maintaining its benefits whether given before, during, or after PCI.
Dr. Deepak L. Bhatt
The study – CHAMPION PHOENIX – was presented at the annual meeting of the American College of Cardiology and published simultaneously in the New England Journal of Medicine (2013; DOI:10.1056/NEJMoa1300815).
The findings shed a more positive light on cangrelor, which fared poorly in two discontinued phase III trials, CHAMPION-PLATFORM, and CHAMPION-PCI; both studies examined the drug’s use in PCI. In 2009, The Medicines Company, which manufactures cangrelor, pulled the plug on both trials after deciding that neither would provide enough positive evidence to pave the way for approval.
In 2012, however, the company published positive results from its BRIDGE trial, finding that cangrelor could effectively maintain anticoagulation for patients who needed to stop their regular antiplatelet therapy while waiting for a non-emergency coronary artery bypass graft.
While neither of the CHAMPION trials met their primary endpoints, both showed positive findings on some secondary endpoints, including stent thrombosis, according to Dr. Deepak L. Bhatt of the Veterans Administration Boston Healthcare System, and his coauthors.
CHAMPION PHOENIX comprised 11,145 patients undergoing either urgent or elective PCI. They were randomized to either a cangrelor/clopidogrel or clopidogrel-only protocol. Patients in the study arm received a cangrelor bolus and infusion, followed by placebo capsules before PCI, and either 300 mg or 600 mg of clopidogrel after (according to the site investigator’s preference). Patients in the comparator group received a placebo bolus and infusion, followed by clopidogrel before PCI and placebo capsules after.
The primary endpoint was a combination of death, myocardial infarction (MI), revascularization because of ischemia, or stent thrombosis at 48 hours after treatment. The secondary endpoint was stent thrombosis at 48 hours. Severe bleeding at 48 hours was the primary safety endpoint.
The patients’ average age was 64 years. Stable angina was the most common indication for PCI (56%). Other indications were non–ST-segment elevation acute coronary syndrome (26%) and ST-segment elevation MI (18%).
The median time from admission to PCI was just over 4 hours. Drug-eluting stents were placed in 56% of the group and bare-metal stents in 42%.
The combined primary endpoint occurred in 5% of the cangrelor group and 6% of the clopidogrel group – a significant 22% risk reduction. The number needed to treat to prevent 1 primary endpoint event was 84.
Stent thrombosis was also significantly less common in the cangrelor group, compared with the placebo group (0.8% vs. 1.4%; OR 0.62).
At 30 days, the incidence of the composite primary endpoint remained significantly lower in the cangrelor group, compared with the placebo group (6% vs. 7%; OR 0.85), as did the incidence of stent thrombosis (1.3% vs. 1.9%; OR 0.68).
The rate of intraprocedural stent thrombosis was also significantly lower in the cangrelor group, compared with the placebo group (0.6% vs. 1%; OR 0.65). Rescue therapy was employed in significantly fewer patients taking cangrelor (2.3% vs. 3.5%; OR 0.65). The rate of procedural complications was also significantly lower in patients taking cangrelor (3.4% vs. 4.5%; OR 0.74).
The rate of severe bleeding was 0.16% in the cangrelor group and 0.11% in the clopidogrel group – not significantly different. Overall, the rate of adverse events was similar, occurring in 20% of cangrelor patients, compared with 19% of clopidogrel patients. However, patients taking the study drug experienced significantly more dyspnea (1.2% vs. 0.3%).
Cangrelor was equally effective in all patient subgroups, the investigators noted.
Cangrelor demonstrated some treatment flexibility. The drug was equally effective in preventing the primary composite endpoint when given before PCI (OR 0.80), during PCI (OR 0.79), or after PCI (OR 0.79). It also worked equally as well for the 75% of patients who received the 600-mg clopidogrel loading dose, as it did for the 25% who received the 300-mg loading dose (OR 0.77 and 0.84, respectively).
The study design specified at least 2 hours of cangrelor infusion; the median infusion time was 129 minutes. But the drug was just as effective in those who had less than 129 minutes, as for those who had more (OR 0.85 and 0.72, respectively).
Cangrelor is a fast-acting ADP P2Y12 inhibitor, achieving an immediate antiplatelet effect, which is maintained as long as the drug is infused. However, its half-life is extremely short – just 3-5 minutes after discontinuation; platelet function normalizes within 1 hour. Because of this, the drug could benefit those who need a short-acting anticoagulant, the authors noted.