Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction
- PMID: 33858620
- DOI: 10.1016/j.jacc.2021.02.049
Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction
Abstract
Background: Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response.
Objectives: This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI.
Methods: The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days.
Results: We randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups.
Conclusions: Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703).
Keywords: ST-segment elevation myocardial infarction; infarct size; inflammation; myocardial salvage; randomized controlled trial; reperfusion injury.
Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Funding Support and Author Disclosures This work was supported by the South-Eastern Norway Regional Health Authority, the Central Norway Regional Health Authority, and Roche. Roche provided the investigational medicinal products and an unrestricted grant. Trial registration number: ClinicalTrials.gov (NCT03004703NCT3004703). Dr. Gullestad has received lecture fees from AstraZeneca, Boehringer Ingelheim, Novartis, and Amgen; and has been a member of the local advisory board in AstraZeneca and Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Comment in
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Inhibiting Interleukin-6 to Reduce Cardiovascular Event Rates: A Next Step for Atherothrombosis Treatment and Prevention.J Am Coll Cardiol. 2021 Apr 20;77(15):1856-1858. doi: 10.1016/j.jacc.2021.02.060. J Am Coll Cardiol. 2021. PMID: 33858621 No abstract available.
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Early inhibition of IL-6 signalling after an acute MI improves myocardial salvage.Nat Rev Cardiol. 2021 Jul;18(7):460. doi: 10.1038/s41569-021-00560-1. Nat Rev Cardiol. 2021. PMID: 33907313 No abstract available.
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Clarification Regarding the Lack of Heart Failure Events in the ASSAIL-MI Trial.J Am Coll Cardiol. 2021 Aug 10;78(6):637. doi: 10.1016/j.jacc.2021.04.105. J Am Coll Cardiol. 2021. PMID: 34353541 No abstract available.
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Reply: Clarification Regarding the Lack of Heart Failure Events in the ASSAIL-MI Trial.J Am Coll Cardiol. 2021 Aug 10;78(6):637-638. doi: 10.1016/j.jacc.2021.06.005. J Am Coll Cardiol. 2021. PMID: 34353542 No abstract available.
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