Smaller Infarct Size with Ticagrelor vs. Clopidogrel in STEMI Patients: Insights from Cardiac MRI

BACKGROUND Ticagrelor has many protective cardiovascular properties in addition to its potent antiplatelet action. This study aims to compare the effects of ticagrelor versus clopidogrel on infarcted mass, quantified by cardiac magnetic resonance imaging (cMRI), in patients with ST-segment elevation acute myocardial infarction (STEMI).

AND RESULTS Adult patients of both sexes with STEMI under pharmaco-invasive strategy were included (n=225). Patients were thrombolized within six hours of symptom onset and underwent angiography and percutaneous coronary interventions, when needed, within the first 24 hours. Before the invasive procedures, patients were randomized to be treated with ticagrelor or clopidogrel (central computerized system). Patients were followed weekly to optimize medical therapy. After 30 days, cMRI was performed and smaller percentage of left ventricular infarcted mass was found with ticagrelor (p=0.012), despite similar angiographic characteristics at baseline (SINTAX score, Gensini score, culprit artery, TIMI flow or myocardial blush). At 30 days, left ventricular ejection fraction (LVEF) was comparable between groups, but 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, in the first day of STEMI.

In patients with STEMI under pharmaco-invasive strategy, therapy with ticagrelor was associated with smaller infarct size than clopidogrel. REGISTRATION URL:https//clinicaltrials.gov; Unique identifier: NCT02428374. Graphical abstract STEMI-ST-elevation myocardial infarction; OMT- Optimal Medical Treatment; cMRI-cardiac magnetic resonance imaging; hsTNT-high-sensitivity troponin T; hsCRP-high-sensitivity C-reactive protein. What Is New? In patients with STEMI under timely pharmaco-invasive strategy, ticagrelor was associated with smaller infarct size by cMRI at day 30 compared with clopidogrel. This beneficial effect was related to lower serum levels of hsTNT and hsCRP at day 1. Randomized patients had similar pre- and post-reperfusion angiographic characteristics, and received optimal medical therapy. What Are the Clinical Implications? Our findings suggest greater benefit of ticagrelor, possibly related to early cardiomyocyte recovery after reperfusion in STEMI patients. Improvement in microcirculation and attenuation in the inflammatory response may have contributed to the findings. Further studies are needed to investigate the underlying mechanisms and potential clinical implications of these findings. Competing Interest Statement The authors have declared no competing interest. Clinical Trial URL:https//clinicaltrials.gov; Unique identifier: NCT02428374. Clinical Protocols https://doi.org/10.1186/s13063-017-2361-1 Funding Statement This study received financial support from the São Paulo Research Foundation, São Paulo, Brazil (FAPESP grant 2012/51692-7), and through an investigator-initiated grant from AstraZeneca (ESR 14-10726). Agencies that partially financed the study: INCT/CNPq Grant 465259/2014-6 and 303001/2019-4), INCT/FAPESP;14/50983-3), INCT/CAPES; 88887.136373/2017-00), FAPESP (Grant 2016/24531-3), and INCT-FCx . Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The local ethics committee approved the study protocol (IRB 0297/2014; CAAE: 71652417.3.0000.5505) which follows the last version of the Helsinki Declaration. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Data referred to in the manuscript can be available upon authorization of the authors.