Acute Myocardial Infarction
Conditions
Keywords
myocardial infarction, percutaneous coronary intervention (PCI), high platelet reactivity (HPR)
Brief summary
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
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.
Interventions
DRUGAspirin 200mg qd, Clopidogrel 2x75mg qd
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)
Sponsors
University Hospital Ostrava
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Platelet inhibition level | 5 days | The main outcome measure is the difference in platelet inhibition between clopidogrel 1x75mg and 2x75mg in HPR patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding Events | 30 days | TIMI major/minor bleeding Bleeding prediction with Crusade bleeding score (calculator free accessible at http://www.crusadebleedingscore.org/index.html) |
| Stent thrombosis | 30 days | 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-- |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ischaemic events (not IST) | 30 days | unplanned targed vessel revascularisation (TVR), need for coronary - aortic by-pass graft ,myocardial infarction |
Countries
Czechia
Outcome results
None listed