Impact of CYP2C19 variant genotypes on clinical efficacy of antiplatelet treatment with clopidogrel: systematic review and meta-analysis

Objective To evaluate the accumulated information from genetic association studies investigating the impact of variants of the cytochrome P450 (CYP) 2C19 genotype on the clinical efficacy of clopidogrel

Which platelet function test is suitable to monitor clopidogrel responsiveness? A pharmacokinetic analysis on the active metabolite of clopidogrel

Background: Multiple platelet function tests claim to be P2Y12-pathway specific and capable of capturing the biological activity of clopidogrel. Objectives: The aim of the present study was to determine which platelet function test provides the best reflection of the in vivo plasma levels of the active metabolite of clopidogrel (AMC). Patients/methods: Clopidogrel-naive patients scheduled for elective percutaneous coronary intervention (PCI) received a 600 mg loading dose of clopidogrel and 100 mg of aspirin. For pharmacokinetic analysis, blood was drawn at 0, 20, 40, 60, 90, 120, 180, 240 and 360 min after clopidogrel loading and peak plasma concentrations (C-max) of the AMC were quantified with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Platelet function testing was performed at baseline and 360 min after the clopidogrel loading. Results: The VASP-assay, the VerifyNow P2Y12-assay and 20 mu mol L-1 adenosine diphosphate (ADP)-induced light transmittance aggregometry (LTA) showed strong correlations with C-max of the AMC (VASP: R2 = 0.56, P <0.001; VerifyNow platelet reactivity units (PRU): R2 = 0.48, P <0.001; VerifyNow %inhibition: R2 = 0.59, P <0.001; 20 mu mol L-1 ADP-induced LTA: R2 = 0.47, P <0.001). Agreement with C-max of the AMC was less evident for 5 mu mol L-1 ADP-induced LTA or whole blood aggregometry (WBA), whereas the IMPACT-R ADP test did not show any correlation with plasmalevels of the AMC. Conclusion: The flow cytometric VASP-assay, the VerifyNow P2Y12 assay and, although to a lesser extent, 20 mu mol L-1 ADP-induced LTA correlate best with the maximal plasma level of the AMC, suggesting these may be the preferred platelet function tests for monitoring the responsiveness to clopidogrel