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Aim: High on-clopidogrel platelet reactivity (HCPR) and high on-aspirin platelet reactivity (HAPR) are associated with atherothrombotic events following coronary stenting. There are, however, few data concerning high on-treatment platelet reactivity to both aspirin and clopidogrel simultaneously. The aim of the present study was to determine the incidence of dual high on-treatment platelet reactivity (DAPR) and its impact on clinical outcome., Methods: On-treatment platelet reactivity was measured in parallel by ADP- and arachidonic acid-induced light transmittance aggregometry (LTA) (n=921) and the point-of-care VerifyNow system (P2Y12 and aspirin) (n=422) in patients on dual antiplatelet therapy undergoing elective stent implantation. HCPR and HAPR were established by receiver-operator characteristic curve analysis. The primary endpoint was a composite of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and ischaemic stroke at 1-year follow-up., Results: The incidence of DAPR varied between 14.7% and 26.9% depending on the platelet function test used. DAPR, assessed by LTA and the VerifyNow system, was highly associated with an adverse clinical outcome. At 1-year follow-up the primary endpoint occurred more frequently in patients with isolated HCPR (11.7%), isolated HAPR (9.6%) or DAPR (10.7%) compared with patients without high on-treatment platelet reactivity (4.2%, all p<0.01) when platelet function was evaluated with LTA. Using the VerifyNow system, patients exhibiting DAPR had the highest risk for the primary endpoint (17.7% vs 4.1% in patients without high on-treatment platelet reactivity, p=0.001)., Conclusions: In patients undergoing elective percutaneous coronary intervention, DAPR to aspirin and clopidogrel is present in one in five patients and is associated with a high risk for atherothrombotic events. DAPR measured by the point-of-care VerifyNow system has a higher predictability for atherothrombotic events than LTA., Clinical Trial Registration Information: www.clinicaltrials.gov: NCT00352014.

Aims: despite treatment with clopidogrel on top of aspirin, stent thrombosis (ST) still occurs being the most serious complication after percutaneous coronary interventions (PCIs). In this study, we aimed to determine the effect of variations in genes involved in the absorption (ABCB1 C1236T, G2677T/A, C3435T), metabolism (CYP2C19*2 and *3, CYP2C9*2 and *3, CYP3A4*1B and CYP3A5*3), and pharmacodynamics (P2Y1 A1622G) of clopidogrel on the occurrence of ST., Methods and Results: the selected genetic variants were assessed in 176 subjects who developed ST while on dual antiplatelet therapy with aspirin and clopidogrel and in 420 control subjects who did not develop adverse cardiovascular events, including ST, within 1 year after stenting. The timing of the definite ST was acute in 66, subacute in 87, and late in 23 cases. The presence of the CYP2C19*2 and CYP2C9*3 variant alleles was significantly associated with ST (OR(adj): 1.7, 95% CI: 1.0-2.6, P = 0.018 and OR(adj): 2.4, 95% CI: 1.0-5.5, P = 0.043, respectively). The influence of CYP2C19*2 (OR(adj): 2.5, 95% CI: 1.1-5.5, P = 0.026) and CYP2C9*3 (OR(adj): 3.3, 95% CI: 1.1-9.9, P = 0.031) was most strongly associated with subacute ST. No significant associations of the other genetic variations and the occurrence of ST were found., Conclusion: carriage of the loss-of-function alleles CYP2C19*2 and CYP2C9*3 increases the risk on ST after PCI.

We evaluated whether the results of light transmittance aggregometry (LTA) differ when "native" platelet-rich plasma (PRP) or adjusted (to a standard platelet count of 250.000/microL) PRP is used in patients on dual antiplatelet therapy with aspirin and clopidogrel. LTA has been performed on the blood of 142 stable angina pectoris patients who were adequately pretreated with aspirin and clopidogrel. Platelet aggregation was significant higher in native PRP as compared to platelet count adjusted PRP (P<0.0001) for all four concentrations of adenosine-5'-diphosphate (ADP) (2, 5, 10 and 20 micromol/L). The interindividual variability was significantly higher in platelet count adjusted PRP as compared to native PRP when stimulated with 10 and 20 micromol/L of ADP. The absolute magnitude of aggregation in non-adjusted PRP is clearly dependent on platelet number. These observations are important since several studies have used empirically defined cut-off levels to segregate non-responders from responders to clopidogrel therapy.

Multiple studies have demonstrated that subgroups of patients receiving combination therapy with aspirin and clopidogrel fail to produce the anticipated antiplatelet effect, and various terms such as 'aspirin resistance', 'clopidogrel resistance', 'heightened post-treatment platelet reactivity' and 'residual platelet reactivity' have been introduced in the medical literature. Light transmittance aggregometry is generally considered to be the gold standard for determining platelet function, but its relevance to in vivo platelet function is questionable and the logistical demands of the method make it impossible to use in daily practice. The introduction of several point-of-care platelet function assays may be the key to the widespread clinical use of platelet function testing and may identify patients who are at risk for the occurrence of adverse cardiac events. In the present paper, we discuss the current commercially available methods of assaying platelet function, including their advantages and limitations and whether they have been shown to correlate with clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract: A simple and rapid point-of-care platelet function assay that guides antiplatelet responses to aspirin and clopidogrel may be of great clinical value for the individual tailoring of therapy. The Plateletworks® assay is based on single platelet counting and has been described as a promising point-of-care assay for the monitoring of the effects of the GP IIb/IIIa antagonists. However, data about its utility and reliability in monitoring the effects of thienopyridines is limited. In the present study we assessed reproducibility of the Plateletworks® assay over time. In addition, a comparison between the Plateletworks® assay and optical aggregometry was performed in a large cohort of patients on maintenance therapy with aspirin and clopidogrel. The Plateletworks® assay demonstrated a good agreement with optical aggregometry in measuring the response to clopidogrel. The results of Plateletworks® are, however, highly time dependent which implicates that measurements should be performed within 10 min. [Copyright &y& Elsevier]