Assessment of P2Y12 inhibition with the point-of-care device VerifyNow P2Y12 in patients treated with prasugrel or clopidogrel coadministered with aspirin
Received 20 May 2008; accepted 26 November 2008. published online 09 February 2009.
Background
Variability in response to thienopyridines has led to the development of point-of-care devices to assess adenosine diphosphate (ADP)-induced platelet aggregation. These tests need to be evaluated in comparison to reference measurements of P2Y12 function during different thienopyridine treatments.
Methods
After a run-in on 75 mg aspirin, 110 subjects were randomized to double-blind treatment with clopidogrel 600 mg loading dose (LD)/75 mg maintenance dose (MD) or prasugrel 60 mg LD/10 mg MD. Antiplatelet effects were evaluated by VerifyNow P2Y12 (VN-P2Y12) device (Accumetrics, San Diego, CA), vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, and light transmission aggregometry (LTA). Prasugrel's and clopidogrel's active metabolite concentration were also determined.
Results
Dose- and time-dependent inhibition of P2Y12 was evident with VN-P2Y12. There was strong correlation with VN-P2Y12 and VASP or LTA for all treatments through a wide range of P2Y12 function. At high levels of P2Y12 inhibition, platelet function measured by VN-P2Y12 was maximally inhibited and could not reflect further changes seen with VASP or LTA methods. Correlation was also observed between exposure to clopidogrel's active metabolite and VN-P2Y12 during MD and LD, whereas it was observed only with prasugrel MD.
Conclusion
The VN-P2Y12 correlated strongly with inhibition of P2Y12 function, as measured with either VASP or LTA. VN-P2Y12 also correlated to exposure to the active metabolite of prasugrel and clopidogrel up to levels associated with assumed saturation of the P2Y12 receptor.
aUppsala Clinical Research Center and Department Medical Sciences and Cardiology, Uppsala University, Sweden
bDepartment of Cardiology, Lund University, Lund, Sweden
dCoagulation Laboratory, Department Medical Sciences, Uppsala, Sweden
Reprint requests: Christoph Varenhorst, MD, Uppsala Clinical Research Center and Department Medical Sciences, Uppsala University Hospital, 751 85 Uppsala, Sweden.
ABSTRACT