Clinical trial NCT03104062: Effect of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients With Acute Myocardial Infarction
Official title: Effect of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients With Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Microvascular Disease
Ticagrelor
Thrombolysis
Microbubble Contrasted Echocardiography
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2017-04-07
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Of the patients diagnosed with ST-segment elevation myocardial infarction (STEMI) who underwent reperfusion therapy and have thrombolysis in myocardial infarction (TIMI) 3 flow, about 40% have flow alterations in the coronary microcirculation, which leads to worse remodeling of the left ventricle with a consequent increase in the mortality of this population. Clopidogrel is the only known antiplatelet medication that brings benefits to the coronary microcirculation. Ticagrelor is significantly superior to clopidogrel in terms of decreasing mortality.

The main objective of this study is to compare the effect of ticagrelor versus clopidogrel on the coronary microcirculation by the Myocardial Perfusion Score Index (MPSI) obtained using Microbubble Contrasted Echocardiography (MCE) in patients who have STEMI and treated with thrombolysis.

Detailed description: The present project should prospectively include patients participating in the TREAT study, who are including individuals with Acute Myocardial Infarction (AMI) treated with fibrinolytic and openly randomized to ticagrelor or clopidogrel within 24 hours of the onset of symptoms. Patients will be submitted to coronary angiography within 4 (± 2) days of the onset of symptoms, and those who, at the end of coronary angiography, present residual obstruction in the culprit vessel of less than 50% and have TIMI 3 flow, regardless of have undergone percutaneous coronary intervention will be included.

Following, on day 2 (± 1) days after coronary angiography (therefore 6 ± 3 days from the onset of symptoms), they will be submitted to microcirculation perfusion evaluation by means of MPSI (myocardial perfusion score index) obtained by MCE (Microbubble contrasted echocardiography) - blood collection for evaluation of Platelet aggregability will be performed immediately prior to the start of MCE. Finally, in order to evaluate left ventricular remodeling, patients will undergo a new Echocardiography within 90 (± 10) days after discharge.

Eligibility criteria: Inclusion Criteria:

* age from 18 years old to 75 years old.
* Patients with a ST-segment elevation AMI with up to 24 hours duration, documented by ischemic symptoms due to atherosclerosis\> 10 minutes at rest, treated with pharmacological thrombolysis, acetylsalicylic acid (ASA) and Clopidogrel or Ticagrelor.
* Cardiac catheterization performed within 4 (± 2) days of the onset of symptoms, which at the end of coronary angiography showed residual obstruction in the "culprit" artery \<50% with TIMI 3 flow regardless of whether or not the percutaneous coronary intervention was performed.

Exclusion Criteria:

* Previous infarction known from the same wall as the current one
* Any contraindication to the use of Clopidogrel or Ticagrelor
* Need for oral anticoagulation therapy or aspirin doses greater than 100mg per day.
* Concomitant oral or intravenous therapy with strong inhibitors of Cytochrome P450, family 3, subfamily A (CYP3A), Substrates of CYP3A with narrow therapeutic indices or strong inducers of CYP3A
* High risk of bradyarrhythmias
* Dialysis therapy
* Clinically important thrombocytopenia known
* Clinically Significant Anemia
* Pregnancy or lactation
* Contraindications to fibrinolytic therapy

Primary outcomes:
measure: Myocardial Perfusion Score Index (MPSI)
timeFrame: 4 (±3) days after Cardiac catheterization
Secondary outcomes:
measure: Left ventricular remodeling 90 days after de AMI, using Echocargiography parameters (End diastolic volume, end systolic volume and ejection Fraction)
timeFrame: after 90 days after discharge
measure: number of myocardial segments with perfusion deficit in coronary microcirculation
timeFrame: 4 (±3) days after Cardiac catheterization
measure: MPSI in patients submitted to angioplasty
timeFrame: 4 (±3) days after Cardiac catheterization
measure: Patients who used clopidogrel prior to randomization and were randomized to ticagrelor
timeFrame: 4 (±3) days after Cardiac catheterization
measure: Elective versus Urgent Percutaneous Coronary Intervention (PCI)
timeFrame: 4 (±3) days after Cardiac catheterization
measure: Platelet aggregability
timeFrame: 4 (±3) days after Cardiac catheterization
measure: Time Ticagrelor or Clopidogrel is administered
timeFrame: 4 (±3) days after Cardiac catheterization
Other outcomes:
measure: Laboratory analysis
timeFrame: 4 (±3) days after Cardiac catheterization
measure: In hospital use of morphine (Yes or No)
timeFrame: 4 (±3) days after Cardiac catheterization
measure: In hospital Use of Proton Pump Inhibitor (PPI) (yes or no)
timeFrame: 4 (±3) days after Cardiac catheterization
Locations:
city: Sao Paulo
country: Brazil
facility: Heart Institute (InCor) - University of Sao Paulo Medical School
Study officials:
References:
citation: Scanavini-Filho MA, Berwanger O, Matthias W, Aguiar MO, Chiang HP, Azevedo L, Baracioli LM, Lima FG, Furtado RHM, Dalcoquio TF, Menezes FR, Ferrari AG, de Luca F, Giugliano RP, Goodman S, Nicolau JC. Effects of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients with Acute Myocardial Infarction. Adv Ther. 2022 Apr;39(4):1832-1843. doi: 10.1007/s12325-022-02061-0. Epub 2022 Feb 26.