Supplement

A10 - Interleukin-1 Blockade in ST-segment Elevation in MI

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Support:The development of this supplement was funded by Abiomed.

Correspondence Details:Antonio Abbate, antonio.abbate@vcuhealth.org

Open Access:

The copyright in this work belongs to Radcliffe Medical Media. Only articles clearly marked with the CC BY-NC logo are published with the Creative Commons by Attribution Licence. The CC BY-NC option was not available for Radcliffe journals before 1 January 2019. Articles marked ‘Open Access’ but not marked ‘CC BY-NC’ are made freely accessible at the time of publication but are subject to standard copyright law regarding reproduction and distribution. Permission is required for reuse of this content.

Background: ST-segment elevation MI (STEMI) is associated with an intense acute inflammatory response. We tested whether interleukin-1 blockade with anakinra significantly reduced the area under the curve for high-sensitivity C-reactive protein levels (CRP-AUC) at 14 days in patients with STEMI.

Methods: We enrolled patients with STEMI within 12 hours of presentation. They were randomly assigned to anakinra 100 mg once daily (standard dose), anakinra 100 mg twice daily (high dose) or placebo for 14 days in a 1:1:1 ratio. Doppler echocardiography studies were obtained at enrolment and 12 months and appraised by a core laboratory blinded to allocation. A dedicated independent committee adjudicated clinical events, including death (D), new-onset heart failure (HF) and hospitalisation for HF (HHF). Log-rank test was used to compare Kaplan–Meier curves.

Results: We randomly assigned 99 subjects to anakinra once daily (n=33), anakinra twice daily (n=31) or placebo (n=35). The CRP-AUC was significantly lower in the anakinra group than in the placebo group (67 [39–120] versus 214 [131–394] mg/day/l, p<0.001), without significant differences between the two anakinra arms, p=0.41). No significant differences were found between anakinra and placebo groups in the interval changes in left ventricular end-systolic volume (+1.4 [−9.8/+9.8] versus −3.9 [−15.4/+1.4] ml, p=0.21) or left ventricular ejection fraction between (+3.9% [−1.6/+10.2] versus +2.7% [−1.8/+9.3], p=0.61). The incidence of D + HF and of D + HHF were significantly lower with anakinra versus placebo (9.4% versus 25.7%, p=0.046, and 0% versus 11.4%, p=0.011, respectively), with no difference between the anakinra arms (p=1.0).

Conclusion: In patients presenting with STEMI, interleukin-1 blockade with anakinra significantly reduces the systemic inflammatory response compared with placebo.