Elsevier

American Heart Journal

Volume 157, Issue 3, March 2009, Pages 562.e1-562.e9
American Heart Journal

Clinical Investigation
Coronary Artery Disease
Assessment of P2Y12 inhibition with the point-of-care device VerifyNow P2Y12 in patients treated with prasugrel or clopidogrel coadministered with aspirin

https://doi.org/10.1016/j.ahj.2008.11.021Get rights and content

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.

Section snippets

Patients and study design

The present study was a prespecified part of a randomized, double-blind, double-dummy, 2-arm, parallel-group study comparing platelet inhibition with prasugrel 60 mg LD/10 mg MD versus clopidogrel 600 mg LD/75 mg MD conducted in adult male and female patients with stable coronary artery disease.13 Subjects visited the research units on 5 different occasions. Blood samples for pharmacodynamic assessment were taken by direct puncture of an antecubital vein at predefined time points and collected

Patients

The 2 treatment groups were not significantly different with respect to demographic and clinical characteristics except a small difference in age (<3 years). Details of the baseline characteristics and clinical events were reported previously.13

Platelet inhibition assessed by the POC device VerifyNow P2Y12

Administration of prasugrel or clopidogrel was associated with a time-dependent inhibition of platelet function, as measured by the VN-P2Y12 device (Figure 1, Table I). As previously reported for LTA and VASP, the 60 mg LD/10 mg MD regimen of prasugrel

Discussion

This study verifies that the POC device, VerifyNow P2Y12, reliably reflects the substantially faster and greater P2Y12 receptor–mediated IPA achieved with prasugrel as compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. As early as 2 hours post-LD, the VN-P2Y12 mean percent inhibition was near maximal and was twice as high with prasugrel 60 mg LD compared with clopidogrel 600 mg LD. During MD, prasugrel 10 mg showed a greater platelet inhibition than

Conclusion

The VN-P2Y12 correlated strongly with inhibition of P2Y12 function, as measured with either VASP or LTA, across a broad range of inhibition levels. However, at very high levels of P2Y12 receptor blockade, VN-P2Y12 did not reflect further changes seen with VASP or LTA. VN-P2Y12 also correlated with exposure to the active metabolite of prasugrel and clopidogrel. Overall, the VN-P2Y12 device, designed to evaluate clopidogrel induced platelet inhibition, might not discriminate among subjects with

Disclosures

Drs Varenhorst, James, Erlinge, Braun, Wallentin, Siegbahn, and Ms Olofsson received an institutional research grant from Daiichi Sankyo Company, Limited, and Eli Lilly and Company to conduct this research. Drs Jakubowski, Brandt, and Winters are employees and stockholders of Eli Lilly and Company. The following employees of Eli Lilly and Company contributed to the paper without co-authorship: Timothy Costigan, PhD (statistical analysis assistance); Vivian Thieu, PhD (writing and administrative

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