Abstract 3996: Intrinsic Platelet Variability in Response to ADP Before Exposure to Thienopyridines Contributes to the Variability in Residual Platelet Reactivity to ADP After Treatment with Clopidogrel or Prasugrel: Results from PRINCIPLE-TIMI 44
Background: Variability in residual platelet function following clopidogrel has been well described. In PRINCIPLE-TIMI 44, a randomized study of prasugrel compared with clopidogrel (600 mg load, 150 mg daily maintenance) in 201 patients undergoing cardiac catheterization for planned PCI, we demonstrated reduced variability and greater inhibition of ADP-stimulated platelet function by prasugrel compared with clopidogrel. In this study, we examined the extent to which intrinsic platelet variability in response to ADP before exposure to thienopyridines contributes to the variability in response after prasugrel and clopidogrel.
Methods: ADP 20 μM stimulated platelet-monocyte aggregates (PMA) and platelet surface P-selectin were measured by flow cytometry pre-treatment, during loading (6 h & 24 h) and maintenance (15 d). To evaluate whether preexistent platelet function predicts post-thienopyridine platelet function, correlations of pre- to post-treatment values were determined by Spearman rank order (rs). VASP and platelet aggregometry with ADP 20 μM were not studied because of uniformity of pre-treatment response to ADP.
Results: Prasugrel resulted in greater platelet inhibition than clopidogrel for each measure. However, for both drugs, pre-treatment reactivity to ADP predicted 6 h (Fig⇓), 24 h and 15 d reactivity to ADP (correlations 0.30 – 0.65).
Conclusion: A patient’s platelet response to ADP before exposure to thienopyridines is directly related to residual platelet reactivity following clopidogrel or prasugrel. Patients hyperresponsive to ADP pre-treatment are more likely hyperresponsive post-treatment - which may be relevant to treatment strategies.