Dataset Information

Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI).

ABSTRACT:

Introduction

Interleukin-6 (IL-6) may be involved in ischaemia-reperfusion injury and myocardial remodelling after myocardial infarction (MI). We have recently shown that IL-6 inhibition by tocilizumab attenuates systemic inflammation and troponin T-release in patients with acute non-ST elevation MI (NSTEMI). Experimental studies suggest that IL-6 inhibition can limit infarct size through anti-inflammatory mechanisms, but this has not been tested in clinical studies. With the ASSessing the effect of Anti-IL-6 treatment in MI (ASSAIL-MI) trial, we aim to examine whether a single administration of the IL-6 receptor antagonist tocilizumab can increase myocardial salvage in patients with acute ST-elevation MI (STEMI).

Methods and analysis

The ASSAIL-MI trial is a randomised, double blind, placebo-controlled trial, conducted at three high-volume percutaneous coronary intervention (PCI) centres in Norway. 200 patients with first-time STEMI presenting within 6 hours of the onset of chest pain will be randomised to receive tocilizumab or matching placebo prior to PCI. The patients are followed-up for 6 months. The primary endpoint is the myocardial salvage index measured by cardiac MRI (CMR) 3-7 days after the intervention. Secondary endpoints include final infarct size measured by CMR and plasma markers of myocardial necrosis. Efficacy and safety assessments during follow-up include blood sampling, echocardiography and CMR.

Ethics and dissemination

Based on previous experience the study is considered feasible and safe. If tocilizumab increases myocardial salvage, further endpoint-driven multicentre trials may be initiated. The ASSAIL-MI trial has the potential to change clinical practice in patients with STEMI.

Registration

Clinicaltrials.gov, identifier NCT03004703.

SUBMITTER: Anstensrud AK

PROVIDER: S-EPMC6803013 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI).

Anstensrud Anne Kristine AK Woxholt Sindre S Sharma Kapil K Broch Kaspar K Bendz Bjørn B Aakhus Svend S Ueland Thor T Amundsen Brage H BH Damås Jan Kristian JK Hopp Einar E Kleveland Ola O Stensæth Knut Haakon KH Opdahl Anders A Kløw Nils-Einar NE Seljeflot Ingebjørg I Andersen Geir Øystein GØ Wiseth Rune R Aukrust Pål P Gullestad Lars L

Open heart 20191015 2

<h4>Introduction</h4>Interleukin-6 (IL-6) may be involved in ischaemia-reperfusion injury and myocardial remodelling after myocardial infarction (MI). We have recently shown that IL-6 inhibition by tocilizumab attenuates systemic inflammation and troponin T-release in patients with acute non-ST elevation MI (NSTEMI). Experimental studies suggest that IL-6 inhibition can limit infarct size through anti-inflammatory mechanisms, but this has not been tested in clinical studies. With the <i>ASS</i>e ...[more]

PMID: 31673391

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Project description:ObjectivesWe hypothesised that patients having experienced one coronary event in their life were susceptible to present differences in their pathways of care and within 1 year of their life courses. We aimed to compare pathways between first-time ST-elevation myocardial infarction (STEMI) and STEMI with prior myocardial infarction (MI).DesignA retrospective observational study based on the Observatoire des Syndromes Coronariens Aigus du réseau RESCUe (OSCAR) registry collecting all suspected STEMI from 10 percutaneous coronary intervention centres in France.SettingAll patients with STEMI from 2013 to 2017 were included (N=6306 with 5423 first-time STEMI and 883 STEMI with prior MI). We provided a matching analysis by propensity score based on cardiovascular risk factors.ParticipantsWe defined first-time STEMI as STEMI occurring at the inclusion date, and STEMI with prior MI as STEMI with a history of MI prior to the inclusion date.ResultsPatients with first-time STEMI and patients with STEMI with prior MI were equally treated during hospitalisation and at discharge. At 12 months, patients with first-time STEMI had a lower adherence to BASIC treatment (ie, beta-blocker, antiplatelet therapy, statin and converting enzyme inhibitor) (48.11% vs 58.58%, p=0.0167), more frequently completed the cardiac rehabilitation programme (44.33% vs 31.72%, p=0.0029), more frequently changed their lifestyle behaviours; more frequently practiced daily physical activity (48.11% vs 35.82%, p=0.0043) and more frequently stopped smoking at admission (69.39% vs 55.00%, p=0.0524). The estimated mortality was higher for patients with STEMI with prior MI at 1 month (p=0.0100), 6 months (p=0.0500) and 1 year (p=0.0600).ConclusionsWe provided an exhaustive overview of the real-life clinical practice conditions of STEMI management. The patients with STEMI with prior MI presented an optimised use of prehospital resources, which was probably due to their previous experience, and showed a better adherence to drug therapy compared with patients with first-time STEMI.Trial registration numberCommission Nationale de l'Informatique et des Libertés (number 2 013 090 v0).

Project description:BackgroundST-segment elevation myocardial infarction (STEMI) still causes significant mortality and morbidity despite best-practice revascularization and adjunct medical strategies. Within the STEMI population, there is a spectrum of higher and lower risk patients with respect to major adverse cardiovascular and cerebral events (MACCE) or re-hospitalization due to heart failure. Myocardial and systemic metabolic disorders modulate patient risk in STEMI. Systematic cardiocirculatory and metabolic phenotyping to assess the bidirectional interaction of cardiac and systemic metabolism in myocardial ischemia is lacking.MethodsSystemic organ communication in STEMI (SYSTEMI) is an all-comer open-end prospective study in STEMI patients > 18 years of age to assess the interaction of cardiac and systemic metabolism in STEMI by systematically collecting data on a regional and systemic level. Primary endpoint will be myocardial function, left ventricular remodelling, myocardial texture and coronary patency at 6 month after STEMI. Secondary endpoint will be all-cause death, MACCE, and re-hospitalisation due to heart failure or revascularisation assessed 12 month after STEMI. The objective of SYSTEMI is to identify metabolic systemic and myocardial master switches that determine primary and secondary endpoints. In SYSTEMI 150-200 patients are expected to be recruited per year. Patient data will be collected at the index event, within 24 h, 5 days as well as 6 and 12 months after STEMI. Data acquisition will be performed in multilayer approaches. Myocardial function will be assessed by using serial cardiac imaging with cineventriculography, echocardiography and cardiovascular magnetic resonance. Myocardial metabolism will be analysed by multi-nuclei magnetic resonance spectroscopy. Systemic metabolism will be approached by serial liquid biopsies and analysed with respect to glucose and lipid metabolism as well as oxygen transport. In summary, SYSTEMI enables a comprehensive data analysis on the levels of organ structure and function alongside hemodynamic, genomic and transcriptomic information to assess cardiac and systemic metabolism.DiscussionSYSTEMI aims to identify novel metabolic patterns and master-switches in the interaction of cardiac and systemic metabolism to improve diagnostic and therapeutic algorithms in myocardial ischemia for patient-risk assessment and tailored therapy.Trial registrationTrial Registration Number: NCT03539133.

Project description:BackgroundOver the past 20 years, the development of regional ST-elevation myocardial infarction (STEMI) care systems has led to remarkable progress in achieving timely coronary reperfusion with attendant improvement in clinical outcomes, including survival. Despite this progress, contemporary STEMI care does not consistently meet the national guideline-recommended goals, which offers an opportunity for further improvement in STEMI outcomes. The lack of single, comprehensive, national STEMI registry complicates our ability to improve STEMI outcomes in particular for high-risk STEMI subsets such as cardiac arrest (CA) and/or cardiogenic shock (CS).ObjectivesTo address this need, the Midwest STEMI Consortium (MSC) was created as a collaboration of 4 large, regional STEMI care systems to provide a comprehensive, multicenter, and prospective STEMI registry without any exclusionary criteria.MethodsThe MSC is a collaboration of 4 large, regional STEMI care systems: Iowa Heart Center in Des Moines, IA; Minneapolis Heart Institute Foundation in Minneapolis, MN; Prairie Heart Institute in Springfield, IL; and The Christ Hospital in Cincinnati, OH. Each has similar standardized STEMI protocol and together include 6 percutaneous coronary intervention (PCI)-capable hospitals and over 100 non-PCI-capable hospitals. Each center had a prospective database that was transferred to a data coordinating center to create the multicenter database. The comprehensive database includes traditional risk factors, cardiovascular history, medications, time to treatment data, detailed angiographic characteristics, and short- and long-term clinical outcomes up to 5-year for myocardial infarction, stroke, and cardiovascular and all-cause mortality. Ten-year mortality rates were assessed by using national death index.ResultsCurrently, the comprehensive database (03/2003-01/2020) includes 14,911 consecutive STEMI patients with mean age of 62.3 ± 13.6 years, female gender (29%), and left anterior descending artery as the culprit vessel (34%). High risk features included: Age >75 years (19%), left ventricular ejection fraction <35% (15%), CA (10%), and CS (8%).ConclusionThis collaboration of 4 large, regional STEMI care systems with broad entry criteria including high-risk STEMI subsets such as CA and/or CS provides a unique platform to conduct clinical research studies to optimize STEMI care.

Dataset Information

Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI).

Introduction

Methods and analysis

Ethics and dissemination

Registration

Publications

Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI).

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