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 in | Netherlands heart journal Vol. 17; no. 5; pp. 195 - 198 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Houten
Bohn Stafleu van Loghum
01.05.2009
|
Subjects | |
Online Access | Get full text |
ISSN | 1568-5888 1876-6250 |
DOI | 10.1007/BF03086246 |
Cover
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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1568-5888 1876-6250 |
DOI: | 10.1007/BF03086246 |