Abstract
BackgroundInadequate 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 P2Y12 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.
MethodsBlood 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.
ResultsThe 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.
ConclusionWe 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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Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands
Department of Clinical Chemistry, St. Antonius Hospital, Nieuwegein, the Netherlands
Department of Cardiology, UMC St Radboud Nijmegen, the Netherlands
Department of Cardiology, St. Antonius Hospital, PO Box 2500, 3435 CM Nieuwegein, the Netherlands
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Bouman, H.J., van Werkum, J.W., Hackeng, C.M. et al. Cangrelor increases the magnitude of platelet inhibition and reduces interindividual variability in clopidogrel-pretreated subjects. NHJL 17, 195–198 (2009). https://doi.org/10.1007/BF03086246
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DOI: https://doi.org/10.1007/BF03086246