Anstensrud AK, et al. Late-Breaking Science in Acute Coronary Syndromes 1. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2020 (virtual meeting).
IL-6 receptor inhibitor improves myocardial salvage in STEMI: ASSAIL-MI
Tocilizumab, an interleukin-6 receptor inhibitor, improved myocardial salvage in patients with first-time acute STEMI compared with placebo, according to the ASSAIL-MI trial presented at the European Society of Cardiology Congress.
“Our findings suggest that IL-6 receptor inhibition is an interesting therapeutic target on top of conventional medical treatment,” Anne Kristine Anstensrud, MD, cardiologist at Oslo University Hospital in Norway, told Healio. “In a subpopulation analysis, patients admitted to hospital within 3 to 6 hours after onset of symptoms were shown to have a benefit of the IL-6 receptor inhibition. Overall, the study medication was safe and well tolerated.”
In this multicenter, randomized clinical trial, researchers analyzed data from 199 patients who presented with 6 hours of chest pain, had ST-segment elevation and were indicated for urgent coronary angiography with the intent to reperfuse a potentially occluded vessel. After hospital admission, patients were randomly assigned a single infusion of tocilizumab (Actemra, Genentech; mean age, 62 years; 79% men) or placebo (mean age, 60 years; 89% men). Both groups received their assigned treatments before undergoing PCI.
“It has been shown with interleukin-6 inhibition with tocilizumab reduces the inflammatory response after NSTEMI and diminishes the release of troponin T particularly in those undergoing PCI, suggesting that tocilizumab can have a protective effect on the ischemia reperfusion injury,” Anstensrud said during the presentation.
The primary endpoint was myocardial salvage index, which was measured by cardiac MRI between 3 and 7 days after randomization. Secondary endpoints included final infarct size after 6 months, area under the receiver operating characteristic curve (AUC) for troponin T during index hospitalization, AUC of C-reactive protein during index hospitalization, and safety and tolerability.
Follow-up was conducted through 6 months and include cardiac MRI, echocardiography and blood samples, in addition to safety measurements.
The myocardial salvage index in patients assigned tocilizumab was 69% compared with 64% in those assigned placebo (adjusted between-group difference, 5.6 percentage points; P = .042).
In a prespecified subgroup analysis, the treatment effect of tocilizumab was greater in patients with symptom onset of more than 3 hours compared with those with symptom onset of 3 hours or less (P for interaction = .034). There was also a trend toward the treatment effect being greater in men than women (P for interaction = .053).
The final infarct size in patients assigned tocilizumab was 12.6 g compared with 15 g in those assigned placebo, but the difference did not reach statistical significance (P = .08). The AUC for troponin T also did not reach statistical significance, although the level was higher in the placebo group compared with the tocilizumab group (2,357 ng/L/h vs. 1,614 ng/L/h; P = .13). The AUC for CRP was lower in the tocilizumab group compared with the placebo group (1.9 mg/L/h vs. 8.6 mg/L/h; P < .001).
“As expected, there was a significant difference in CRP [favoring] tocilizumab,” she said.
Other factors did not differ between both groups including N-terminal pro-B-type natriuretic peptide, left ventricular end-diastolic volume, serious adverse events and infections requiring hospitalization.
“The ASSAIL-MI trial was a phase 2 trial,” Anstensrud said in an interview. “Further research is needed both to evaluate the effect in a larger study population according to clinical endpoints, but also to select patients that might have the most beneficial effect of the anti-inflammatory treatment.”