Cangrelor in Patients Undergoing Coronary Stent Procedures

San Francisco—Patients undergoing coronary stent procedures who received cangrelor had a significant, 22% odds reduction in the primary end point of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis compared with a group that received clopidogrel, according to a randomized, double-blind, double-dummy, superiority trial. The benefit was maintained for 30 days, and there was no difference in severe bleeding or transfusions, according to Deepak L. Bhatt, MD, the study’s lead author, who presented the data in a late-breaking clinical trial session at the ACC meeting. Results were simultaneously published online in the New England Journal of Medicine [10.1056/NEJMoa1300815].

At 48 hours, 4.7% of patients in the cangrelor group had died or had myocardial infarction, ischemia-driven revascularization, or stent thrombosis compared with 5.9% of patients in the clopidogrel group (odds ratio [OR]; 95% confidence interval [CI], 0.66-0.93; P=.005). In addition, 0.8% of patients who received cangrelor had stent thrombosis at 48 hours compared with 1.4% of patients who received clopidogrel (OR, 0.62; 95% CI, 0.43-0.90; P=.01).

There was no significant difference in severe bleeding at 48 hours: 0.16% of patients in the cangrelor group and 0.11% of patients in the clopidogrel group (OR, 1.50; 95% CI, 0.53-4.22; P=.44).

The Medicines Company, the drug’s manufacturer, funded the trial and noted it would file for FDA approval based on the findings of this trial as well as an earlier trial. Dr. Bhatt noted the study’s authors used off-label drugs and investigational agents, including clopidogrel and cangrelor.

Antiplatelet therapy is common in percutaneous coronary intervention, but available oral agents are limited because of their relatively long duration of action and bioavailability, according to Dr. Bhatt. Cangrelor, an intravenous adenosine diphosphate receptor antagonist, did not meet its primary end point in 2 previous trials, although the drug significantly reduced stent thrombosis at 48 hours in 1 study and led to no excessive severe bleeding.

In the CHAMPION (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) PHOENIX study, the authors enrolled 10,900 patients at 153 sites in 12 countries. Patients had stable angina, non-ST segment elevation acute coronary syndrome, or ST segment elevation myocardial infarction, and were P2Y₁₂ inhibitor-naïve.

Patients were randomized to receive cangrelor bolus and infusion plus a placebo pill or placebo bolus and infusion plus 300 mg to 600 mg of oral clopidogrel. The treatment lasted for 2 hours or the duration of the procedure, whichever was longer. At the end of the infusion, the cangrelor group took 600 mg of oral clopidogrel, while the placebo group received oral placebo.

At baseline, the demographics in the groups were similar. Mean age was 64 years, 28% were female, and 37% lived in the United States.

After 48 hours of treatment, 3.8% of patients in the cangrelor group had myocardial infarction compared with 4.7% of patients in the clopidogrel group (OR, 0.80; 95% CI, 0.67-0.97; P=.02). There was no significant difference in deaths, as 0.3% of patients in each group died after 48 hours of treatment (OR, 1.00; 95% CI, 0.52-1.92; P>.99)

At 30 days, 6.0% of patients in the cangrelor group had died or had myocardial infarction, ischemia-driven revascularization, or stent thrombosis compared with 7.0% of patients in the clopidogrel group (OR; 95% CI, 0.73-0.99; P=.03). In addition, 1.3% of patients who received cangrelor had stent thrombosis at 30 days compared with 1.9% of patients who received clopidogrel (OR, 0.68; 95% CI, 0.50-0.92; P=.01).

Further, after 30 days of treatment, 4.1% of patients in the cangrelor group had myocardial infarction compared with 5.0% of patients in the clopidogrel group (OR, 0.82; 95% CI, 0.68-0.98; P=.03). There was no significant difference in deaths, as 1.1% of patients in the cangrelor group and 1.0% of patients in the clopidogrel group had died after 30 days of treatment (OR, 1.09; 95% CI, 0.76-1.58; P>.64).