Reducing Micro Vascular Dysfunction in Acute Myocardial Infarction by Ticagrelor

Study Overview
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Brief Summary
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The current trial will compare the protective effect of ticagrelor and prasugrel on microvascular dysfunction in patients with revascularized ST elevation myocardial infarction.

Detailed Description
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Coronary microvascular dysfunction is highly prevalent in revascularized ST-elevation myocardial infarction and has important prognostic implications. Current data suggest that ticagrelor might be superior to prasugrel in the reduction of coronary microvasculature dysfunction. Thus, we have designed a clinical trial that will compare microvascular function in revascularized ST-elevation myocardial infarction patients at treatment steady state with ticagrelor or prasugrel. Coronary microvascular dysfunction will be assessed with the index of microcirculatory resistance after primary percutaneous coronary intervention and at 1 month follow-up in the infarct-related vessel and non-infarct related vessel.

Official Title
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Reducing Micro Vascular Dysfunction In Revascularized ST-elevation Myocardial Infarction Patients by Off-target Properties of Ticagrelor

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Prasugrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent Patients presenting with ST-elevation myocardial infarction <12 hours after symptom onset Successful percutaneous coronary intervention of the infarct-related vessel with a modern drug-eluting stent Intermediate stenosis in non-infarct-related vessel (50-90%) Exclusion Criteria: history of myocardial infarction Participation in another clinical study with an investigational product during the preceding 30 days history of cerebrovascular accident (CVA) or 'transient ischaemic attack' (TIA) History of intracranial haemorrhage indication or use of oral anticoagulant therapy (i.e. acenocoumarol) severe liver dysfunction (Child-Pugh score 10-15) congestive heart failure cardiogenic shock left ventricular ejection fraction < 35% bleeding diathesis age ≥ 75 or < 18 body weight < 60 kg gout coagulation disorders severe pulmonary disease pregnancy and breast feeding limited life expectancy platelet count < 100 000/mm3 history of drug addiction or alcohol abuse in the past 2 years need for chronic nonsteroidal anti-inflammatory drug creatinine clearance <30 mL/min or dialysis chronic total occlusion (CTO) Left main disease allergy or contra-indication for ticagrelor or prasugrel Contra-indication for adenosine Patients unable to be followed on-site Unable to undergo or contra-indications for MRI Contra-indication for drug-eluting stent Inability to obtain informed consent Coronary artery bypass grafting in medical history

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticagrelor<br>Ticagrelor 90 mg twice a day, tablet Duration: 1 year after PCI | Drug: Ticagrelor<br>* After a standard loading dose of 180 mg ticagrelor in the ambulance (before primary PCI), patients will receive a maintenance dose of ticagrelor 90 mg twice a day for 1 year.<br>* Other names: Brilique;|
| Active Comparator: Prasugrel<br>Prasugrel 10 mg once a day, tablet Duration: 1 year after PCI | Drug: Prasugrel<br>* After a standard loading dose of 180 mg ticagrelor in the ambulance (before primary PCI), patients will receive a single loading dose of prasugrel 60 mg (1 day after standard loading dose ticagrelor),followed by a maintenance dose of prasugrel 10 mg once a day for 1 year.<br>* Other names: Efient;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Index of microcirculatory resistance (IMR) | measured in the infarct-related artery | 1 month after primary PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta Index of microcirculatory resistance (IMR) | measured in the infarct-related artery and non-infarct related artery | Baseline vs. 1 month follow-up | 
| The reactive hyperemia index (RHI) |  | 1 month and 1 year after primary PCI | 
| Myocardial salvage | measured with MRI | 1 month after primary PCI | 
| Left ventricular ejection fraction (LVEF) recovery | measured with MRI | 1 month after primary PCI | 
| Microvascular obstruction | measured with MRI | 3 days after primary PCI | 
| Asymmetric Dimethylarginine (ADMA) levels | Blood measurements | 1 month after primary PCI | 
| Intra-myocardial haemorrhage | measured with MRI | 3 days after primary PCI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ST elevation myocardial infarction, Percutaneous coronary intervention, Endothelial function, Ticagrelor, Prasugrel