Effect of Ticagrelor and Clopidogrel on Coronary Microcirculation in Patients With Acute Myocardial Infarction

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.

Study Overview

• Status: Completed
• Conditions: Coronary Microvascular Disease; Thrombolysis; Ticagrelor; Microbubble Contrasted Echocardiography
• Intervention / Treatment: Diagnostic test: Microbubble Contrasted Echocardiography; Diagnostic test: Platelet Aggregability; Diagnostic test: Laboratory

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403000
    • Heart Institute (InCor) - University of São Paulo Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Ticagrelor; Patients will be randomized to have Ticagrelor 90mg BID	Diagnostic test: Microbubble Contrasted Echocardiography; Myocardial Perfusion Score Index (MPSI) obtained using Microbubble Contrasted Echocardiography; Diagnostic test: Platelet Aggregability; Obtained using Multiplate Analyzer; Diagnostic test: Laboratory; it will be collected at patients arrival, Reative C-Protein, BNP, CK-mass, Troponine, interleukine-6, Creatinine.
Other: Clopidogrel; Patientes will be randomized to have Clopidogrel 75mg once a day	Diagnostic test: Microbubble Contrasted Echocardiography; Myocardial Perfusion Score Index (MPSI) obtained using Microbubble Contrasted Echocardiography; Diagnostic test: Platelet Aggregability; Obtained using Multiplate Analyzer; Diagnostic test: Laboratory; it will be collected at patients arrival, Reative C-Protein, BNP, CK-mass, Troponine, interleukine-6, Creatinine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial Perfusion Score Index (MPSI)	Obtained using Microbubble Contrasted Echocardiography	4 (±3) days after Cardiac catheterization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular remodeling 90 days after de AMI, using Echocargiography parameters (End diastolic volume, end systolic volume and ejection Fraction)	To compare the parameters of left ventricular remodeling (End diastolic volume, End Systolic Volume, Ejection Fraction) at after 90 days after discharge from the ticagrelor and clopidogrel groups	after 90 days after discharge
number of myocardial segments with perfusion deficit in coronary microcirculation	To evaluate the number of myocardial segments with perfusion deficit in coronary microcirculation in the ticagrelor and clopidogrel groups	4 (±3) days after Cardiac catheterization
MPSI in patients submitted to angioplasty	To evaluate MPSI in the subgroups of patients submitted to angioplasty and not submitted to angioplasty	4 (±3) days after Cardiac catheterization
Patients who used clopidogrel prior to randomization and were randomized to ticagrelor	To evaluate MPSI in subgroups of patients who used clopidogrel prior to randomization and were randomized to ticagrelor	4 (±3) days after Cardiac catheterization
Elective versus Urgent Percutaneous Coronary Intervention (PCI)	To compare the ticagrelor and clopidogrel groups in patients who had elective or urgent PCI	4 (±3) days after Cardiac catheterization
Platelet aggregability	To evaluate the platelet aggregability in the ticagrelor and clopidogrel groups obtained immediately before Myocardial Contrasted Echocardiography (MCE) by Multiplate	4 (±3) days after Cardiac catheterization
Time Ticagrelor or Clopidogrel is administered	Evaluate the main objective of the study in two subgroups: 1) Ticagrelor or Clopidogrel administered less than 12 hours from the symptoms onset. 2) greater than or equal to 12 hours from the symptoms onset	4 (±3) days after Cardiac catheterization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Laboratory analysis	Number of Participants With Abnormal Laboratory Values in both groups, Ticagrelor and Clopidogrel. The laboratory analysis will be: Platelet count; Platelet mean volume; HbA1C; Creatinine clearance; Reactive c-protein; Interleucine-6; Brain natriuretic peptide (BNP); Troponin; Creatine Kinase-MB (CK-MB);	4 (±3) days after Cardiac catheterization
In hospital use of morphine (Yes or No)	Evaluate MPSI in patients who used Morphine or not.	4 (±3) days after Cardiac catheterization
In hospital Use of Proton Pump Inhibitor (PPI) (yes or no)	Evaluate MPSI in patients who used PPI or not	4 (±3) days after Cardiac catheterization

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 1, 2018

Study Registration Dates

• First Submitted: March 17, 2017
• First Submitted That Met QC Criteria: March 31, 2017
• First Posted (Actual): April 7, 2017

Study Record Updates

• Last Update Posted (Actual): May 18, 2018
• Last Update Submitted That Met QC Criteria: May 15, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Angina Pectoris; Myocardial Infarction; Infarction; Microvascular Angina
• Other Study ID Numbers: 4416

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No