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. 2023 Aug;386(2):156-163.
doi: 10.1124/jpet.123.001601. Epub 2023 Apr 10.

Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction

Marco Giuseppe Del Buono  1 , Juan Ignacio Damonte  1 , Francesco Moroni  1 , Juan Guido Chiabrando  1 , Roshanak Markley  1 , Jeremy Turlington  1 , Cory R Trankle  1 , Le Kang  1 , Giuseppe Biondi-Zoccai  1 , Michael C Kontos  1 , Charlotte S Roberts  1 , Benjamin W Van Tassell  2 , Antonio Abbate  2
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Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction

Marco Giuseppe Del Buono et al. J Pharmacol Exp Ther. 2023 Aug.

Abstract

Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has been shown to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI. We sought to determine whether time-to-treatment influences the efficacy of anakinra on systemic inflammation and incidence of HF events in patients with STEMI. We divided the cohort in two groups base6d on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF. We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271 (182-391) minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with time from PCI to treatment <271 minutes (222.6 [103.9-325.2] vs. 78.4 [44.3-131.2], P < 0.001) and those with time from PCI to treatment ≥271 minute (235.2 [131.4-603.4] vs. 75.5 [38.9-171.9], P < 0.001) (P > 0.05 for interaction). Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment <271 minutes (5 [11%] vs. 9n[36%], log-rank χ 2 5.985, P = 0.014) as well as in patients with time from PCI to drug ≥271 minutes (2n[5%] vs. 7 [23%], log-rank χ 2 3.995, P = 0.046) (P > 0.05 for interaction). IL-1 blockade with anakinra blunts the acute systemic inflammatory response and prevents HF events independent of time-to-treatment. SIGNIFICANCE STATEMENT: In patients with ST segment elevation presenting within 12 hours of pain onset and treated within 12 hours of reperfusion, interleukin-1 blockade with anakinra blunts the acute systemic inflammatory response, a surrogate of interleukin-1 activity, and prevents heart failure events independent of time-to-treatment.

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Figures

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Graphical abstract
Fig. 1.
Fig. 1.
Differences in AUC-CRP between patients receiving placebo versus anakinra according to time from PCI to investigational treatment. Differences in AUC-CRP between patients receiving placebo versus anakinra in those with time from PCI to investigational treatment below the median and above the median. AUC-CRP, area-under-the-curve for C reactive protein; PCI, percutaneous coronary intervention.
Fig. 2.
Fig. 2.
Correlation analysis between AUC-CRP and time from PCI to treatment. Correlation analysis between AUC-CRP and time from PCI to treatment showing no correlation in patients receiving anakinra. AUC-CRP, area-under-the-curve for C reactive protein; PCI, percutaneous coronary intervention.
Fig. 3.
Fig. 3.
Differences in AUC-CRP in patients receiving placebo versus anakinra according to CRP levels at baseline. in those with CRP levels at baseline below the median or above the median. AUC-CRP, area-under-the-curve for C reactive protein; PCI, percutaneous coronary intervention.
Fig. 4.
Fig. 4.
Effect on anakinra on the combined endpoint of death or new onset HF. Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment below the median as well as in patients with time from PCI to drug above the median. HF, heart failure; PCI, percutaneous coronary intervention.
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References

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