Debra L. Beck, MSc and Eugene Braunwald, MD
In patients with ST-segment elevation myocardial infarction (STEMI), prompt revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes. Because up to 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response, Broch et al sought to evaluate the effect of the interleukin-6 receptor (IL-6) inhibitor tocilizumab on myocardial salvage in acute STEMI.
In ASSAIL-MI, 199 patients admitted with STEMI within 6 hours of symptom onset were randomly assigned to receive a single infusion of 280 mg tocilizumab or matching placebo. All were treated at 3 high-volume PCI centers in Norway.
The primary endpoint was the myocardial salvage index as measured by cardiac magnetic resonance imaging 3 to 7 days after intervention, and showed a benefit for tocilizumab compared to placebo (adjusted between-group difference, 5.6 percentage points; p=0.04).
The benefit of tocilizumab on the primary outcome appeared to be limited to patients presenting >3 hours after symptom onset (p=0.034). Also, men appeared to benefit more than women (p=0.053).
Median final infarct size measured at 6 months was 21% lower in the tocilizumab arm, but this difference did not reach statistical significant (7.2% vs. 9.1%; p=0.08). Microvascular obstruction was less extensive in the tocilizumab arm (p=0.03) and there was a significant reduction in C-reactive protein during hospitalization (p<0.001), but no difference in N-terminal pro-B-type natriuretic peptide or cardiac troponin.
There were small increases in atherogenic lipids, triglycerides, and liver enzymes with tocilizumab—all known effects of the drug—but adverse events were mostly mild and evenly distributed across the treatment groups.
Summary
In this small trial, treatment with tocilizumab given within 6 hours of symptom onset increased myocardial salvage in patients with acute STEMI.
Comments
In an editorial, Dr. P Ridker wrote that tocilizumab moves beyond IL-6 blockade as done in CANTOS to a downstream approach of inhibiting IL-6 and “represents a logical next scientific step in the development of anti-inflammatory therapies…” he wrote. Meanwhile, while the science progresses, there are immediate strategies that clinicians can adopt, namely encouraging exercise, smoking cessation, and following a healthy diet, all of which reduce C-reactive protein and IL-6.
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Very useful information for clinicians interested in prevention , clinical outcome and early adoption of new scientific knowledge,