253Effects of Interleukin-1 blockade with Anakinra on cardiac function in ST-segment elevation acute myocardial infarction: results from the VCUART3 echocardiography study
Authors: Abbate A , Kadariya D , Medina De Chazal H , Chiabrando J G , Trankle C R , Abraham Foscolo M M , Wohlford G F , Carbone S , Buckley L F , Lipinski M J , Appleton D , Abouzaki N A , Turlington J S , Van Tassell B W 
Published: October 2019

Abstract

Background
ST-segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response further promoting cardiac dysfunction and heart failure (HF). Pilot proof-of-concept studies with anakinra, recombinant Interleukin-1 (IL-1) receptor antagonist, have shown feasibility and safety of IL-1 blockade in patients with STEMI. In the current study we analyzed the effects of anakinra on left ventricular (LV) dimensions and function in patients with STEMI.

Methods
We enrolled patients with STEMI within 12 hours of presentation at 3 sites in the United States of America. After revascularization, patients were randomly assigned to receive anakinra 100 mg twice daily, anakinra 100 mg once daily alternated with placebo once daily every 12 hours, or placebo twice daily, for 14 days in a 1:1:1 ratio. A transthoracic echocardiogram was completed within 24 hours of admission and at 1 year follow up to measure LV end-diastolic and end-systolic volumes (LVEDV and LVESV, respectively), stroke volume (SV) and ejection fraction (LVEF). (ClinicalTrials NCT01950299)

Results
Paired echocardiography studies (follow up study obtained 362 days [336–375] after the baseline study) were available in 63 of the 99 patients (63%): 23 of 35 patients in the placebo group (66%) and 40 of the 64 patients in the anakinra group (62%, P>0.05 for missing studies between the 2 groups; P>0.05 for duration of follow up). Baseline LVEDV, LVESV, SV and LVEF was not significantly different comparing placebo and anakinra (all P>0.05). Patients treated with anakinra had a significant improvement in LVEF from 49.8% (41.8–60.0%) to 54.0% (46.0–58.4%, P=0.028) and SV from 43.6 ml (37.6–52.1 ml) to 48.7 ml (40.9–62.5 ml, P=0.008), whereas no significant changes occurred within the placebo group (LVEF: from 51.7% [40.1–56.0%] to 53.5% [43.4–59.4%], P=0.25; SV: from 47.7 ml [40.1–56.8 ml], to 53.0 ml [44.9–57.4 ml], P=0.81). The between-groups differences, however, were not statistically significant. No significant changes were noted in LVEDV and LVESV in either group. The interval changes in CRP between admission and 72 hours, expression of the acute inflammatory response, inversely correlated with the LVEF at follow up (R=-0.30, P=0.026), with higher levels of CRP corresponding to lower LVEF values

Conclusions
A significant improvement in cardiac systolic function was seen in patients treated with IL-1 receptor antagonist, anakinra, following STEMI, and not in patients with placebo. Further studies are however required to determine whether the benefits of IL-1 blockade in the prevention and treatment of HF are mediated by the effects on cardiac function.

Acknowledgement/Funding
Funded by NHLBI 1R34HL121402; Drug supply from Swedish Orphan Biovitrum