Efficacy and Safety of Individualized P2Y12 Receptor Antagonists Treatment Based on Agregometry Versus Fixed Dose Regimen in Patients After Acute Myocardial Infarction
Condition: Acute Coronary Syndrome; STEMI; NSTEMI - Non-ST Segment Elevation MI; PLATELET AGGREGATION; INDIVIDUALIZED THERAPY
MeSH terms: Myocardial Infarction; Acute Coronary Syndrome; Infarction
Study type: Interventional
Phase: Phase 4

Summary: 
      The specific goal of this study is to determine whether the individualized approach and
      adjusting the dosage of the P2Y12 receptor inhibitors will improve the platelet inhibiton and
      the clinical outcome in patients with an ACS, that were treated with PCI and the
      aforementioned drugs, but with an increased initial residual platelet activity. It is
      expected that the patients that have undergone the P2Y12 inhibitor therapy adjustment
      (according to the platelet reactivity measured by POC devices) will have better clinical
      outcomes (ie less ischemic events, without a significant increase in bleeding events) than
      those who did not undergo the therapy adjustment.
    

Detailed description: 
      In this study we plan to continue our previous research on individualized approach to
      platelet aniaggregation therapy in patients with an ACS treated with a PCI. The subjects
      included in this study will be adult patients successfully treated in our department for ACS
      (unstabile angina pectoris, non-ST segment elevation myocardial infarction and ST segment
      elevation myocardal infarction) with a PCI, a coronary stent implantation and the subsequent
      dual platelet antiaggregation therapy combining ASA and a P2Y12 receptor inhibitor. The
      diagnosis of different types of ACS will be made depending on the clinical presentation, ECG
      findings and changes in cardiac biomarker serum levels (troponin T and MB creatinine kinase
      isoezyme). Percutaneous coronary revascularization and the dual platelet antiaggregation
      therapy are the basis of the modern ACS treatment. Because the newer P2Y12 receptor
      inhibitors are not momentarily widely available in Croatia, the initial treatment will
      include the combination of ASA and clopidogrel. The exclusion critera are as following:
      postinterventional continuous GPIIb/IIIa inhibitor therapy, thrombocytopenia (<150x10E9/L),
      signifcant renal failure (creatinine>200 µmol/L), anemia (Htc<30%), hemorrhagic diathesis,
      history of recent hemorrhagic or ischemic CVI (within 6 months of admission), recent surgical
      procedure (within 6 weeks of admission) and an indication for chronic anticoagulant therapy.
      Also patients older than 80 years of age will not be included into this study. The necessary
      number of subjects is between 100 and 120.

      Aggregometry using the ADP test will be done to all the patients without the exclusion
      criteria that were successfully treated wth PCI. The testing will be done within 24 hours of
      the intervention in order to determine the pharmacodynamic effect P2Y12 receptor inhibitors
      have on platelets and their reactivity. The optimal platelet reactivity (according to the
      international consensus) is between 19 and 46 U (49). The patients that will have an
      increased residual PR (>46 U) after being given the loading doses of clopidogrel will be
      included in this study and randomized into three groups using a computer software (Research
      Randomizer). The patients randomized into the first group will be given the newer P2Y12
      receptor inhibitor ticagrelor during the 12 months. The second group of patients will be
      given ticagrelor initially, and after the first 30 days it will be replaced with clopidogrel,
      that will be given for the remaining time period (up to 12 months). Clopidogrel dosing will
      be modified according to the results of the aggregometry using the ADP test. The third group
      of patients will have the same therapy regiment as the second group, but will be given the
      standard doses of clopidogrel regardless of the aggregometry findings. The follow-up period,
      during which the dual platelet antiaggregation therapy will be administered, is going to be
      12 months for each patient. Within this time-frame, total of ten PR measurements will be
      done. The measurements in the first month are scheduled as follows: on the first, second,
      third, seventh and thirtieth day after the ACS and the PCI. The following measurements are
      scheduled two, three, six, nine and twelve months after the ACS and the PCI.
    

Intervention name(s): Clopidogrel; Ticagrelor
Intervention type(s): Drug; Drug
Intervention description(s): Adjusting clopidogrel dosage according to platelet reactivity results during 12 months after PCI; Administration of standard dose of ticagrelor during 12 months after PCI
Intervention MeSH terms: Clopidogrel; Ticagrelor
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment