Cangrelor increases the magnitude of platelet inhibition and reduces interindividual variability in clopidogrel-pretreated subjects

Background Inadequate platelet inhibition despite aspirin and clopidogrel therapy during and after a percutaneous coronary intervention is associated with an impaired clinical outcome. Cangrelor, a direct and reversible P2Y 12 inhibitor that is currently in development, has the potential to achieve...

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Published inNetherlands heart journal Vol. 17; no. 5; pp. 195 - 198
Main Authors Bouman, H. J., van Werkum, J. W., Hackeng, C. M., Clappers, N., Berg, J. M. ten
Format Journal Article
LanguageEnglish
Published Houten Bohn Stafleu van Loghum 01.05.2009
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ISSN1568-5888
1876-6250
DOI10.1007/BF03086246

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Summary:Background Inadequate platelet inhibition despite aspirin and clopidogrel therapy during and after a percutaneous coronary intervention is associated with an impaired clinical outcome. Cangrelor, a direct and reversible P2Y 12 inhibitor that is currently in development, has the potential to achieve higher levels of inhibition of ADP-induced platelet aggregation than clopidogrel. The aim of the present study was to compare the magnitude of platelet inhibition in clopidogrel-pretreated patients before and after the in vitro addition of a subtherapeutic dose of cangrelor. Methods Blood samples were drawn from patients pretreated with clopidogrel and aspirin who were undergoing elective percutaneous coronary intervention (n=39). Platelet function analysis with ‘classical’ light transmittance aggregometry (both peak and late aggregation [at 6 min]) was performed before and after the in vitro addition of cangrelor (0.25 μmol/l) to platelet-rich plasma (PRP). After an incubation period of five minutes, platelet aggregation was induced by 5 and 20 μmol/l ADP. Results The in vitro addition of 0.25μmol/l cangrelor to the PRP from clopidogrel-treated subjects resulted in an additional reduction in ADP-induced platelet aggregation. For ADP concentrations of 5 and 20 μmol/l, peak aggregation showed a decrease of 75 and 85%, respectively (p<0.001 for both), while late aggregation was almost completely diminished (p=0.003 and p<0.001, respectively). Furthermore, the interindividual variation in inhibition of ADP-induced platelet aggregation by clopidogrel was greatly reduced after the addition of cangrelor. Conclusion We demonstrate that the in vitro addition of even a subtherapeutic dose of cangrelor to the PRP of clopidogrel-pretreated patients results in an additional reduction of ADP-induced platelet aggregation. Moreover, cangrelor was able to diminish the interindividual variation observed in clopidogrel-inhibited platelet aggregation. ( Neth Heart J 2009;17:195–8.)
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ISSN:1568-5888
1876-6250
DOI:10.1007/BF03086246