Effect of platelet inhibition with cangrelor during PCI on ischemic events

The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects.

In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guideline-recommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours.

The rate of the primary efficacy end point was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (adjusted odds ratio with cangrelor, 0.78; 95% confidence interval [CI], 0.66 to 0.93; P=0.005). The rate of the primary safety end point was 0.16% in the cangrelor group and 0.11% in the clopidogrel group (odds ratio, 1.50; 95% CI, 0.53 to 4.22; P=0.44). Stent thrombosis developed in 0.8% of the patients in the cangrelor group and in 1.4% in the clopidogrel group (odds ratio, 0.62; 95% CI, 0.43 to 0.90; P=0.01). 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%). The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups.

Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding. (Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.).