Downstream Molecular Signals of P2Y12 Receptors in Hyporeactive Patients Under Clopidogrel Treatment A Possible Mechanism of HOTPR(High On-Treatment Platelet Reactivity)
Condition: Stable Angina
MeSH terms: Angina, Stable
Study type: Observational

Summary: 
      The investigators designed the following experiment to observe the pattern of administration
      in vitro, which can be completely excluded liver enzyme cytochrome P450 metabolism under the
      influence and observe the relevant P2Y12 receptor downstream signal changes, hope in the
      above experiments, that the human body directly for the difference between the existence of
      drug reactions exist.
    

Detailed description: 
      Platelet reactivity has been accepted as an indicator of the reaction of the P2Y12 inhibitor
      during treatment, currently, the existing evidence to support the post-treatment platelet
      activity can be used to distinguish the potential risk among patients who received
      percutaneous transluminal coronary angioplasty after ischemic / thrombotic events. The risks
      of stent thrombosis, of which, by analysis of the PRU (P2Y12 reaction units) value level of
      VerifyNow System has been considered an international standard tools. PRU value by VerifyNow
      system can easily and quickly showed platelet reactivity relative to short or long term risk
      stratification under dual antiplatelet agents(aspirin and clopidogrel) after stents
      implantation. High PRU response units (drug poor responders) in accordance with the 2013
      publication of the European Society of Cardiology guidelines defined of platelet function, is
      PRU not less than 208(≥208).

      The investigators ran a previous related plan within 2014 under the medical study project
      budget of the Taipei City hospital, which named "platelet reactivity as a post-percutaneous
      coronary stent implantation antiplatelet adjust the reference", it has been figured that
      responsibility under the P2Y12 receptor inhibitors were significantly different between the
      taiwanese and Caucasians (taiwanese revealed clopidogrel lower responsive, but stronger
      reaction to ticagrelor), although "low" response to clopidogrel between taiwanese (In fact,
      according to our experiments, 30 days after medication, the rate of HOTPR-High On- Treatment
      Platelet Reactivity; namely PRU≥208, the taiwanese and Caucasians are very close to each),
      but it has relative lower subacute stent thrombosis rate than the Caucasian at 30 days(This
      reaction is also known as the "Asian paradox" ), according to literature known abroad because
      of the high prevalence of CYP2C19 point gene deletion rate among the Asians (compare with
      Caucasians: ~ 65% vs ~ 30%); there also suggested other possible explanations: Caucasian
      factor V Leiden (G1691A) and prothrombin (G20210A) a higher proportion of mutations, on
      hemostatic factors (fibrinogen, d-dimer, and factor VIII) and plasma endothelial activation
      markers (such as von Willebrand factor, intercellular adhesion molecule 1, and E-selectin)
      existed differences between the races; in addition, a number of different indicators of
      inflammation, such as CRP. Asians show lower level CRP than the Caucasians. However, did the
      investigators found the true answer? So, the investigators designed the following experiment,
      through the mode of drug administration in vitro, can completely exclude the influence of the
      liver metabolic enzyme cytochrome P450, and observe the relevant downstream signals of P2Y12
      receptors. The investigators believed through the current study, the internal differences in
      drug responsibility can be clarified.
    

Intervention name(s): clopidogrel; Placebos
Intervention type(s): Drug; Drug
Intervention description(s): routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit); no medication, healthy subjects.
Intervention MeSH terms: Clopidogrel
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        stable angina who received routine dual antiplatelet agents therapy.
      
Biospecimen description: 
      downstream molecular signals of P2Y12 receptor in the platelet(Platelet Rich Plasma).
    
Keywords: PRU; P2Y12 receptor