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Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial
Kaspar Broch1, Anne Kristine Anstensrud2, Sindre Woxholt3
1Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, University of Oslo, Oslo, Norway.
Insights
Tocilizumab improved myocardial salvage in ST-segment elevation myocardial infarction (STEMI) patients. This interleukin-6 receptor inhibitor shows promise in reducing reperfusion injury after prompt percutaneous coronary intervention (PCI).
Area of Science:
- Cardiology
- Immunology
- Pharmacology
Background:
- Prompt percutaneous coronary intervention (PCI) reduces infarct size in ST-segment elevation myocardial infarction (STEMI) but reperfusion injury causes significant myocardial loss.
- Inflammatory responses, including interleukin-6 (IL-6), contribute to myocardial damage post-STEMI.
Purpose of the Study:
- To evaluate the efficacy of tocilizumab, an IL-6 receptor inhibitor, in preserving myocardial tissue in acute STEMI patients.
- To assess the impact of tocilizumab on myocardial salvage index (MSI) following PCI for STEMI.
Main Methods:
- The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled study involving 199 STEMI patients.
- Patients received either tocilizumab or placebo infusion shortly after STEMI diagnosis and PCI.
- Myocardial salvage index was measured using cardiac MRI 3–7 days post-treatment.
Main Results:
- Tocilizumab significantly increased the myocardial salvage index compared to placebo (5.6 percentage points, p=0.04).
- Reduced microvascular obstruction was observed in the tocilizumab group.
- No significant difference in final infarct size was found between the groups (p=0.08).
Conclusions:
- Tocilizumab enhances myocardial salvage in patients experiencing acute STEMI.
- The findings suggest a potential therapeutic role for IL-6 inhibition in mitigating reperfusion injury after STEMI.
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).
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