Abstract 13354: Pharmacodynamic Effects of Cangrelor and Clopidogrel: The Platelet Function Substudy from the Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition in Patients Undergoing Percutaneous Coronary Intervention (CHAMPION-PCI) Trial
Background: A prospectively designed platelet function substudy in the CHAMPION-PCI trial was performed in a selected cohort of patients to provide insight into the pharmacodynamic effects of cangrelor, particularly in regard to whether cangrelor therapy may interfere with the inhibitory effects of clopidogrel.
Methods: This substudy was conducted in a subset of patients randomized in the CHAMPION-PCI trial comparing cangrelor with 600 mg of oral clopidogrel administered before percutaneous coronary intervention. Pharmacodynamic measures included platelet reactivity units (PRU) assessed by VerifyNow P2Y12 testing (primary endpoint marker), platelet aggregation by light transmittance aggregometry following 5 and 20 adenosine diphosphate stimuli, and markers of platelet activation determined by flow cytometry. The primary endpoint was the percentage of patients who achieved < 20% change in PRU between baseline and > 10 hours after PCI.
Results: The main study was stopped early limiting enrollment in the platelet substudy which included a total of 234 subjects, of whom 167 had pharmacodynamic assessments for the primary endpoint. The percent of individuals achieving < 20% change in PRU between baseline and >10 hours after PCI in the cangrelor arm (32/84, 38.1%) compared with theclopidogrel arm (21/83, 25.3%) was not statistically significant (difference: 12.79%, 95% CI: -1.18%, 26.77%; p=0.076). All pharmacodynamic markers as well as the prevalence of patients with high on-treatment platelet reactivity were significantly lower during infusion in patients treated with cangrelor compared with clopidogrel. A rapid platelet inhibitory effect was achieved during cangrelor infusion and a rapid offset of action after treatment discontinuation without any pharmacodynamic interaction when transitioning to clopidogrel.
Conclusions: This CHAMPION platelet substudy represent the largest pharmacodynamic experience with cangrelor. The findings demonstrate cangrelor's potent inhibitory effect on the P2Y12 receptor, its rapid onset and offset, and the lack of pharmacodynamic interaction when transitioning to clopidogrel therapy.
- © 2011 by American Heart Association, Inc.