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Assessment of P2Y(12) inhibition with the point-of-care device VerifyNow P2Y12 in patients treated with prasugrel or clopidogrel coadministered with aspirin

Varenhorst, Christoph; James, Stefan; Erlinge, David LU ; Braun, Oscar LU ; Brandt, John T.; Winters, Kenneth J.; Jakubowski, Joseph A.; Olofsson, Sylvia; Wallentin, Lars and Slegbahn, Agneta (2009) In American Heart Journal 157(3).
Abstract
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 P2Y(12) function during different thienopyridine treatments. Methods After a run-in on 75 mg aspirin, I 10 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... (More)
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 P2Y(12) function during different thienopyridine treatments. Methods After a run-in on 75 mg aspirin, I 10 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 P2Y(12) was evident with VN-P2Y12. There was strong correlation with VN-P2Y12 and VASP or LTA for all treatments through a wide range of P2Y(12) function. At high levels of P2Y(12) 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-F`2Y12 during MD and LD, whereas it was observed only with prasugrel MD. Conclusion The VN-P2Y12 correlated strongly with inhibition of P2Y(12) 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 P2Y(12) receptor. (Am Heart J 2009; 1 57:562.e1-562.e9.) (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Heart Journal
volume
157
issue
3
publisher
Mosby
external identifiers
  • wos:000264214700024
  • scopus:60749105720
ISSN
1097-6744
DOI
10.1016/j.ahj.2008.11.021
language
English
LU publication?
yes
id
65e8bf7e-03be-4092-893c-cdada4fe17dd (old id 1405129)
date added to LUP
2009-06-15 09:59:07
date last changed
2017-11-12 03:21:36
@article{65e8bf7e-03be-4092-893c-cdada4fe17dd,
  abstract     = {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 P2Y(12) function during different thienopyridine treatments. Methods After a run-in on 75 mg aspirin, I 10 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 P2Y(12) was evident with VN-P2Y12. There was strong correlation with VN-P2Y12 and VASP or LTA for all treatments through a wide range of P2Y(12) function. At high levels of P2Y(12) 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-F`2Y12 during MD and LD, whereas it was observed only with prasugrel MD. Conclusion The VN-P2Y12 correlated strongly with inhibition of P2Y(12) 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 P2Y(12) receptor. (Am Heart J 2009; 1 57:562.e1-562.e9.)},
  author       = {Varenhorst, Christoph and James, Stefan and Erlinge, David and Braun, Oscar and Brandt, John T. and Winters, Kenneth J. and Jakubowski, Joseph A. and Olofsson, Sylvia and Wallentin, Lars and Slegbahn, Agneta},
  issn         = {1097-6744},
  language     = {eng},
  number       = {3},
  publisher    = {Mosby},
  series       = {American Heart Journal},
  title        = {Assessment of P2Y(12) inhibition with the point-of-care device VerifyNow P2Y12 in patients treated with prasugrel or clopidogrel coadministered with aspirin},
  url          = {http://dx.doi.org/10.1016/j.ahj.2008.11.021},
  volume       = {157},
  year         = {2009},
}