Downstream Molecular Signals of P2Y12 Receptors in Hyporeactive Patients Under Clopidogrel Treatment A Possible Mechanism of HOTPR(High On-Treatment Platelet Reactivity)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Downstream Molecular Signals of P2Y12 Receptors in Hyporeactive Patients Under Clopidogrel Treatment (A Possible Mechanism of HOTPR:High On- Treatment Platelet Reactivity)

Conditions
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Stable Angina

Intervention / Treatment
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* Drug: clopidogrel
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DAPT(Dual antiplatelet therapy) after regular stent implantation. Exclusion Criteria: allergy to DAPT(Dual antiplatelet therapy). major bleeding intolerance to DAPT(Dual antiplatelet therapy).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| group 1<br>placebo control without medication. | Drug: Placebos<br>* no medication, healthy subjects.<br>|
| group 2<br>hyper-reactive responser after clopidogrel. | Drug: clopidogrel<br>* routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)<br>|
| group 3<br>hypo-reactive responser after clopidogrel. | Drug: clopidogrel<br>* routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)<br>|
| group 4<br>normo-reactive responser after clopidogrel. | Drug: clopidogrel<br>* routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)<br>|
| group 5<br>reaction after OPC-13013 | Drug: clopidogrel<br>* routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)<br>|
| group 6<br>reaction after AR-C | Drug: clopidogrel<br>* routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)<br>|
| group 7<br>reaction after simastatin | Drug: clopidogrel<br>* routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PRU(Platelet Rreactivity Unit) 24 Hours After DAPT(Dual AntiPlatelet Therapy) Western Blot After Medication | PRU(Platelet Rreactivity Unit) 24 hours after DAPT(Dual AntiPlatelet Therapy) Western blot after medication | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PRU, P2Y12 receptor