Original Investigation
Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction

https://doi.org/10.1016/j.jacc.2021.02.049Get rights and content
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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)

Key Words

inflammation
infarct size
myocardial salvage
randomized controlled trial
reperfusion injury
ST-segment elevation myocardial infarction

Abbreviations and Acronyms

CMR
cardiac magnetic resonance imaging
CRP
C-reactive protein
IL
interleukin
I/R
ischemia/reperfusion
MI
myocardial infarction
NT-proBNP
N-terminal pro-B-type natriuretic peptide
PCI
percutaneous coronary intervention
STEMI
ST-segment elevation myocardial infarction
TnT
cardiac troponin T

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The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

Drs. Broch and Anstensrud are co-first authors.

Drs. Aukrust and Gullestad are joint last authors.