REsistance to Aspirin and Clopidogrel in acuTe Myocardial Infarction

Study Overview
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Brief Summary
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The purpose of this study is to compare 3 point-of-care methods for monitoring antiplatelet therapy to golden standard (Light transmittance aggregometry-LTA) in high risk population of acute myocardial infarction patients. If two methods (PFA-100, VerifyNOW,Multiplate or LTA) will indicate insufficient antiplatelet blockade/high residual reactivity for aspirin, clopidogrel or both, the dose of aspirin will be increased to 200mg qd and the dose of clopidogrel will be increased to 2x75mg qd.In addition genotyping of CYP2C19 (6 alleles) will be performed.

Detailed Description
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Dual antiplatelet therapy is the cornerstone of treatment of coronary heart disease after coronary stent implantation. The interindividual response to this therapy is not uniform, however. There are subgroups of patients, where no anticipated antiplatelet effect to either aspirin, clopidogrel or both is reached. The term of aspirin/clopidogrel resistance has been introduced few years ago, most recently it was substituted by more suitable term - high on-treatment residual platelet reactivity (HPR). Although there are many assays to monitor antiplatelet therapy, uncertainty still remains about the correlation of HPR with ischemic vascular events (in-stent thrombosis, myocardial infarction, etc.). Thus platelet aggregation testing is considered to be the most promising method to indicate inappropriate/low response to aspirin/clopidogrel, however the best suited method is not established yet. Up-to date light transmittance aggregometry is widely accepted as golden standard, nonetheless labour intensive and difficult to standardize. On the other hand many point-of-care aggregation testing methods like PFA-100, VerifyNOW, Multiplate etc. have been introduced, their role in clinical practice is uncertain, however. The biggest challenge of today is to determine platelet function assay, which could reliably indicate future ischemic vascular events;moreover it could be potentially used to tailor antiplatelet therapy and precede these events. It was demonstrated, that gene polymorphism - CYP2C19*2 and CYP2C9*3 loss of function is conjugated with an increased occurrence of stent thrombosis. Within the project we also plan to examine 4 alleles which have not been examined in detail before.

Official Title
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Phase IV Study of Aspirin and Clopidogrel Therapy Tailored by Functional Thrombocyte Examination (PFA-100, LTA and VerifyNOW) in Acute Myocardial Infarction

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Drug: Aspirin 200mg qd, Clopidogrel 2x75mg qd


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: acute myocardial infarction (verified by troponin I elevation and ST-segment deviation ≥0.1mV in ≥2 contiguous ECG leads persisting for at least 20 minutes and angiographical proof of coronary stenosis ) preceding antiplatelet medication with aspirin100mg qd/5 and more days before PCI pre-treatment with 600mg Clopidogrel loading dose preferably patients with drug eluting stent implantation signed informed consent Exclusion Criteria: stable/unstable angina pectoris active malignancy contraindication to antiplatelet therapy increased risk of bleeding (trauma, surgery or non-ischemic stroke in last month) effective anticoagulation therapy:LMWH, Pradaxa, Xarelto, Warfarin known thrombophile disorder SIRS renal insufficiency (eGFR under 15ml/min) severe anemia (<80 g/l) polyglobulia (>160 g/l) pregnancy Hematocrit <0.25 > 0.55

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard therapy<br>standard dose of 100mg aspirin qd and 1x75mg Clopidogrel will be given | |
| Active Comparator: ASA/CLP increase<br>According to 2 platelet monitoring assays HPR confirmation aspirin will be increased to 200mg qd, clopidogrel to 2x75mg qd | Drug: Aspirin 200mg qd, Clopidogrel 2x75mg qd<br>* According to 2 platelet monitoring assays HPR confirmation aspirin will be increased to 200mg qd, clopidogrel to 2x75mg qd. This treatment will be given for 30 days from index event (myocardial infarction)<br>* Other names: R-130964;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet inhibition level | The main outcome measure is the difference in platelet inhibition between clopidogrel 1x75mg and 2x75mg in HPR patients | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding Events | TIMI major/minor bleeding Bleeding prediction with Crusade bleeding score (calculator free accessible at http://www.crusadebleedingscore.org/index.html) | 30 days | 
| Stent thrombosis | In-stent thrombosis will be assessed in 30-days time-frame in all patients included in the trial. -- due to inadequate power of the trial IST cannot be primary outcome measure-- | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myocardial infarction, percutaneous coronary intervention (PCI), high platelet reactivity (HPR)