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

• Published in: The American heart journal Vol. 157; no. 3; pp. 562.e1 - 562.e9
• Main Authors: Varenhorst, Christoph, James, Stefan, Erlinge, David, Braun, Oscar O, Brandt, John T, Winters, Kenneth J, Jakubowski, Joseph A, Olofsson, Sylvia, Wallentin, Lars, Siegbahn, Agneta
• Format: Journal Article
• Language: English
• Published: United States 01.03.2009
• Subjects: Anticoagulants - administration & dosage; Aspirin - administration & dosage; Cardiac and Cardiovascular Systems; Clinical Medicine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Monitoring - instrumentation; Drug Therapy, Combination; Female; Humans; Kardiologi; Klinisk medicin; Male; Medical and Health Sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Optical Rotation; Phosphorylation; Piperazines - therapeutic use; Point-of-Care Systems; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Thiophenes - therapeutic use; Ticlopidine - administration & dosage; Ticlopidine - analogs & derivatives
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2008.11.021

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. 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. 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-P2Y12 during MD and LD, whereas it was observed only with prasugrel MD. 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.