DOI: 10.5061/dryad.8pk0p2p1v
title: Data from: CMR study comparing antiplatelet therapies in STEMI patients

description: Ticagrelor has many protective cardiovascular properties beyond potent
 antiplatelet action. This study aimed to compare the effects of ticagrelor
 versus clopidogrel on infarcted mass, quantified by cardiac magnetic
 resonance (CMR), in patients with ST-segment elevation acute myocardial
 infarction (STEMI). Adult patients of both sexes with STEMI under a
 pharmaco-invasive strategy were included (n=225). Patients were treated by
 thrombolysis within six hours of symptom onset and underwent angiography
 with percutaneous coronary interventions, when needed, within the first 24
 hours. Prior to the invasive procedures, patients were randomly assigned
 to receive either ticagrelor or clopidogrel using a centralized
 computerized system. Patients were followed on a weekly basis to optimize
 their medical therapy. After 30 days, CMR was performed and a smaller
 percentage of left ventricular infarcted mass was found with ticagrelor
 (p=0.012), despite similar angiographic findings at baseline (Syntax
 score, Gensini score, culprit artery, TIMI flow, and myocardial blush). At
 30 days, left ventricular ejection fraction (LVEF) was comparable between
 groups. Still, the K-means algorithm displayed more homogeneous responses
 for smaller infarcted mass and better LVEF among those patients treated
 with ticagrelor. Standard lipid panel and most inflammatory parameters
 were similar at baseline and after 30 days. However, lower
 high-sensitivity troponin T and high-sensitivity C-reactive protein levels
 were found in samples collected from patients treated with ticagrelor on
 the first day of STEMI. In patients with STEMI under a pharmaco-invasive
 strategy, therapy with ticagrelor was associated with a smaller infarct
 size than clopidogrel.
description: The CONSORT checklist is available as a supplementary
 file. <strong>Ethics
 approval</strong> The study protocol was approved
 by the local ethics committee (IRB 0297/2014; CAAE: 71652417.3.0000.5505),
 which follows the last version of the Helsinki Declaration. All patients
 signed the informed consent prior to any study procedure.
 <strong>Study design</strong> The
 comparison between ticagrelor and clopidogrel in patients with STEMI is
 part of a thematic study with pre-specified analyses that also included
 two lipid-lowering strategies. The study design, including objectives and
 inclusion/exclusion criteria, was previously published. Briefly, the
 BATTLE-AMI study (NCT02428374) is a prospective, randomized, open-label
 clinical trial with blinded CMR and angiographic analyses. Adult STEMI
 patients who underwent thrombolytic therapy were included. After providing
 written informed consent, eligible patients were randomized in a 1:1 ratio
 to receive either ticagrelor or clopidogrel using a centralized
 computerized system before coronary angiography.
 <strong>Patient Recruitment and
 Treatment</strong> Consecutive STEMI patients of
 both sexes, aged 18-75 years, were treated by tenecteplase
 (Metalyse<sup>Ò</sup>, Boehringer Ingelheim) in the first 6
 hours of symptom onset, according to patients' weight, and received
 300 mg of clopidogrel and 300 mg of aspirin in public hospitals of the
 city of São Paulo, Brazil, as part of the SP STEMI treatment network. In
 the network routine, patients were subsequently transferred to a tertiary
 teaching hospital and underwent systematic early invasive coronary
 angiography. Thus, the patients of the study were referred to our
 university hospital in the first 24 hours, and randomly assigned 1:1 to
 either ticagrelor (Brilinta<sup>Ò</sup>, Astrazeneca) 90 mg
 b.i.d. after a loading dose of 180 mg or clopidogrel
 (Plavix<sup>Ò</sup>, Sanofi) 75 mg q.d. with an additional
 loading dose of 300 mg of clopidogrel at the discretion of the attending
 physician. Coronary angiography was performed in all patients in the first
 24 hours, and PCI, when needed, in the culprit lesion. Additional coronary
 interventions in non-culprit lesions were performed at the same time or
 electively according to the hemodynamic team's decision. All these
 interventions conform to the recommended guidelines. As part of the
 BATTLE-AMI study, patients were randomized to receive rosuvastatin 20 mg
 (Crestor<sup>Ò</sup>, Astrazeneca) or simvastatin 40 mg
 combined with ezetimibe 10 mg (Vytorin<sup>Ò</sup>, MSD).
 Patients with clinical instability, previous myocardial infarction or
 coronary revascularization, severe renal insufficiency, active liver
 disease, immune diseases, or known intolerance to the study drugs were
 excluded. Thirty days after STEMI, a CMR was performed. Patients were
 included from May 2015 to March 2020. All laboratory, angiographic, or CMR
 analyses were performed blindly.
 <strong>Laboratory analysis</strong>
 Blood samples were collected on the first day, or in the morning
 of the next day, in case of overnight hospital admission, and also after
 30 days. Routine laboratory parameters were performed
 in the central laboratory of the university hospital. B and T Lymphocyte
 subtypes were examined by flow cytometry as previously reported.
 Circulating cytokines were determined by enzyme-linked immunosorbent assay
 (ELISA). <strong>Quantitative Coronary
 Angiography</strong> An independent angiographic
 core laboratory assessed quantitative coronary angiography blinded to
 randomization assignment and clinical outcomes for baseline and post-PCI
 lesions with the use of validated quantitative methods (CMS; Medis Medical
 Imaging Systems, Leiden, The Netherlands). The path line, vessel contour,
 lumen, reference diameters, and lesion length were determined
 automatically by the contrast density, occasionally requiring editing by
 analysts. The following parameters were obtained through quantitative
 coronary angiography: (i) minimal lumen diameter; (ii) reference vessel
 diameter; (iii) obstruction length; (iv) percent diameter stenosis.
 Rentrop score, TIMI flow, myocardial blush, and the corrected TIMI frame
 count grades in the infarcted vessel were defined as previously reported.
 Each lesion with ≥50% diameter stenosis in vessels ≥1.5 mm was scored
 using the syntax score algorithm (https://syntaxscore.org/), fully described elsewhere. <strong>Cardiac Magnetic Resonance</strong> In 3.0 T clinical scanners (Siemens, Erlangen, Germany, Philips), patients remained in the supine position, and a phased-array receiver cardiac coil was placed on the chest. Cine images were ECG-gated and were acquired with approximately 8 sec breath holds for each slice. Cine images were acquired in the short-axis view (from the mitral valve insertion plane through the left ventricle until the apex) and three long-axis views. Slice thickness was 8 mm, and slice spacing was 2 mm. All indexes studies were done with the injection of a commercially available gadolinium-based contrast agent (gadopentetate dimeglumine or gadoteridol) administered intravenously at a dose of 0.2 mmol per kilogram of body weight, and a dynamic, breath-hold MR first-pass perfusion examination were obtained and resulted in three short-axis slices of 8–10 mm thickness were acquired every heart beat along the long axis, with spatial resolution of 2–3 × 2–3 mm. Stress data were acquired following 6 min of dipyridamole (0.56 mg/min/kg intravenous), followed by an aminophylline injection to reverse hyperemia. A rest injection of the same contrast agent (0.2 mmol per kilogram of body weight) was done to obtain images that would be compared with those of the stress phase. After a 5-minute delay to allow for washout of the contrast agent from healthy myocardium, magnitude and phase-sensitive inversion recovery images following an inversion recovery pulse were recorded to allow the detection of late gadolinium enhancement. These were registered in the same views used for cine MRI and used to assess for myocardial viability. The inversion time suggested by the protocol could be adjusted by the technologist to optimize image quality. Typical voxel size was 1.9 by 1.4 by 8 mm. Scanning protocol for the follow-up study included segmented cine CMR (short and long axis views) for cardiac function, followed by segmented late gadolinium enhancement imaging for viability. Myocardial infarction size was quantified by manual contouring of the late gadolinium enhancement areas in each of the short-axis slices, using dedicated software, as described elsewhere. <strong>Study endpoints and predictor definitions</strong> The primary objective of the study was to compare the amount of infarcted myocardial mass measured by CMR after 30 days of treatment with ticagrelor or clopidogrel, among STEMI patients under the pharmaco-invasive strategy. A secondary objective was the left ventricular ejection fraction (LVEF). Circulating inflammatory cells and biochemical variables were also examined. <strong>Statistical analysis</strong> All analyses were made using software R Core Team (2024), and the level of significance was stated at 5%. Data was reported as median and interquartile range or mean and standard deviation. Qualitative variables were reported as numbers and percentages. The Shapiro-Wilk test was used to examine normality. The Mann-Whitney test was used to compare nonparametric variables for independent groups, including myocardial fibrosis (% and g), and LVEF. Categorical variables were compared by the Pearson's Chi-square test or Fisher's exact test. Correlations between variables were examined by the Spearman's Rho test. The K-means algorithm was used for cluster analysis involving LVEF and myocardial fibrosis. Sensitivity analysis was conducted for infarcted mass and LVEF using Multivariate Imputation by Chained Equations in the R software.
description: # Data from: CMR study comparing antiplatelet therapies in STEMI patients
 Dataset DOI: [10.5061/dryad.8pk0p2p1v](10.5061/dryad.8pk0p2p1v) ##
 Description of the data and file structure CMR collected after 30 days
 post-STEMI ### Files and variables #### File:
 Dryad_Dataset_Revised_(1)03092025.xlsx **Description:**  **Variables**
 Gender, Age Group Group: Study group identifier (e.g., treatment/control).
 Lipid-lowering therapy: Whether the patient is on lipid-lowering
 medication (e.g., statins). Antiplatelet therapy: Use of antiplatelet
 drugs (e.g., aspirin, clopidogrel). Diabetes status: Diabetes
 classification (1 = no, 2 = type 1, 3 = type 2). Weight: Patient’s body
 weight (kg). Hypertension: Presence of high blood pressure (1 = yes, 2 =
 no). Day 1 hs troponin: T High-sensitivity troponin T levels on day 1
 (biomarker for cardiac injury). Systolic blood pressure: Systolic BP
 (mmHg). Diastolic blood pressure: Diastolic BP (mmHg). Smoking status of
 the patient. Heart rate: Heart rate (beats per minute). LDL, HDL, Total
 cholesterol, Triglycerides Lipid profile measurements (mmol/L or mg/dL).
 HbA1c Glycated hemoglobin (indicator of long-term blood glucose).
 Creatinine, eGFR Kidney function measures. Lesion site, Lesion length
 Characteristics of the coronary artery lesion treated. % stenosis:
 Percentage of vessel narrowing before PCI (angiographic measure). Stenotic
 Flow Reserve - PRE PCI Coronary flow reserve before percutaneous coronary
 intervention. Proximal Stent Diameter, Distal Stent Diameter Diameter of
 the stent at proximal and distal ends (mm). Reference Diameter
 (Interpolated) post Reference vessel diameter post-procedure. Minimal
 Stent Diameter The smallest diameter within the stented segment post-PCI.
 Stent Length Total length of the implanted stent (mm). % Stenosis Post PCI
 Residual vessel narrowing after PCI (%). Stenotic Flow Reserve - post PCI
 Coronary flow reserve after PCI — indicator of success. # Code/software
 Excel can be used to view the file ## Human subjects data Data was
 anonymized and followed the requirements of the Ethics Committee of
 UNIFESP. All patients included in the study agreed to participate in the
 study and signed the informed consent before any study procedure. The
 study was approved by the Ethics Committee of Universidade Federal de São
 Paulo (UNIFESP), registered as IRB 0297/2-14 CAAE: 7165417.3.0000.5505.