• Interventional Techniques & Devices
• Myocardial Infarction
• Cardiology Clinical Trials
• Thrombotic Disorders

• Interventional Techniques & Devices
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• Myocardial Infarction
• Cardiology & Cardiovascular Medicine
• Cardiology Clinical Trials
• Thrombotic Disorders

Cangrelor, an intravenous, potent, direct-acting adenosine diphosphate (ADP) receptor antagonist, significantly reduced the composite endpoint of death, myocardial infarction (MI), ischemia-driven revascularization, and stent thrombosis in patients undergoing percutaneous coronary intervention (PCI) with no excess in severe bleeding compared with clopidogrel loading at the time of PCI.

The Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [CHAMPION PHOENIX; Bhatt DL et al. N Engl J Med 2013] followed 2 prior studies of cangrelor, CHAMPION PLATFORM [Bhatt DL et al. N Engl J Med 2009] and CHAMPION PCI [Harrington RE et al. N Engl J Med 2009], 2 large Phase 3 trials that had been stopped early when an interim analysis concluded that the trials were unlikely to show that cangrelor was superior to clopidogrel. Deepak L. Bhatt, MD, MPH, Harvard Medical School, Boston, Massachusetts, USA, presented the results of the CHAMPION PHOENIX study in a late-breaking clinical trial.

Cangrelor is a rapidly acting (half-life of 3 to 6 minutes), reversible and intravenous ADP receptor antagonist that permits return to normal platelet function within one hour after discontinuation. These characteristics have spurred interest in its use in the setting of PCI. The CHAMPION PHOENIX trial was a randomized, double-blind, double-dummy, superiority study conducted globally at 153 sites in 12 countries [Bhatt DL et al. N Engl J Med 2013]. The primary efficacy endpoint was the composite of death, MI, ischemia-driven revascularization, and stent thrombosis at 48 hours. Secondary endpoints included the incidence of stent thrombosis at 48 hours, and efficacy endpoints were examined at 30 days. The primary safety endpoint was GUSTO severe bleeding at 48 hours.

Patients with stable angina, non-ST-elevation acute coronary syndrome or ST-elevation MI (STEMI; n=10,900) requiring PCI who were included in the study. Eligible patients could not have received pretreatment with a P2Y12 inhibitor prior to angiography or at any time within 7 days prior to randomization. Once suitability for PCI was confirmed by either angiography or STEMI diagnosis, patients were randomly assigned to 2 arms: Group A received a cangrelor bolus and infusion (30 μg/kg, 4 μg/kg/min) and placebo clopidogrel for the duration of the procedure with a minimum duration of 2 hours and a maximum duration of 4 hours, then clopidogrel 600 mg after the end of the infusion; Group B received placebo bolus and infusion along with active clopidogrel with the loading dose chosen by the investigator (300 or 600 mg) [Bhatt DL et al. N Engl J Med 2013].

The study population had a median age of 64 years, were mostly male (72%), the majority were enrolled with stable angina (56%), and most (74%) received a 600-mg loading dose of clopidogrel [Bhatt DL et al. N Engl J Med 2013]. Treatment with cangrelor significantly reduced the primary endpoint compared with clopidogrel (4.7% vs 5.9%; OR, 0.78; 95% CI, 0.66 to 0.93; p=0.005).

There was no difference with respect to mortality or for ischemia-driven revascularization, but MI was significantly less frequent with cangrelor (3.8% vs 4.7%; OR, 0.80; 95% CI, 0.67 to 0.97; p=0.02). Subgroup analyses showed consistency of benefit with no significant heterogeneity, with the exception of patients with peripheral artery disease (n=832; p for interaction=0.003) in whom cangrelor appeared to have a nominally more robust benefit. Efficacy results were similar when extended out to 30 days. There were no significant excess in GUSTO severe bleeding (0.16% vs 0.11%; OR, 1.5; 95% CI, 0.53 to 4.22; p=0.44) or transfusions (p=0.16); however, there was more ACUITY major bleeding (4.3 vs 2.5; OR, 1.72; 95% CI, 1.39 to 2.13; p<0.001) with cangrelor compared with clopidogrel. Transient dyspnea occurred more frequently in the cangrelor group (1.2% vs 0.3%; p<0.001).

Limitations of this study include the use of a 300-mg clopidogrel loading dose in 1405 patients in the comparator arm (although results were consistent after adjustment for loading dose), the use of clopidogrel as the comparator instead of the more rapidly acting and potent later generation agents prasugrel and ticagrelor, and the exclusion of patients who were pretreated with clopidogrel prior to angiography. No economic analyses have been presented to-date, and this will remain an important consideration should cangrelor become available for clinical use.

Although patients pretreated with ADP receptor blockers were excluded, the findings support a strategy where treatment with potent anti-platelet therapy may not be necessary prior to delineation of coronary anatomy, which may be beneficial for patients subsequently determined to need urgent surgery. In addition, this intravenous therapy presents an option for patients unable to take oral medications. Dr. Bhatt concluded that intravenous cangrelor might offer an attractive option across the full spectrum of PCI, including stable angina, non-STEMI, and STEMI.

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