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. 2022 Aug 11;8(5):503-510.
doi: 10.1093/ehjcvp/pvab075.

Interleukin-1 blockade with anakinra and heart failure following ST-segment elevation myocardial infarction: results from a pooled analysis of the VCUART clinical trials

Antonio Abbate  1 , George F Wohlford  1 , Marco Giuseppe Del Buono  1 , Juan Guido Chiabrando  1 , Roshanak Markley  1 , Jeremy Turlington  1 , Dinesh Kadariya  1 , Cory R Trankle  1 , Giuseppe Biondi-Zoccai  2   3 , Michael J Lipinski  1 , Benjamin W Van Tassell  1
Affiliations

Interleukin-1 blockade with anakinra and heart failure following ST-segment elevation myocardial infarction: results from a pooled analysis of the VCUART clinical trials

Antonio Abbate et al. Eur Heart J Cardiovasc Pharmacother. .

Abstract

Aims: ST-segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). In this study, we sought to evaluate the effect of anakinra, a recombinant interleukin-1 receptor antagonist, on the incidence of HF.

Methods and results: We performed a pooled analysis of three early phase randomized clinical trials. The endpoints included the composite of all-cause death and new-onset HF, and the composite of all-cause death and hospitalization for HF at 1-year follow-up. Safety events, including injection site reaction and serious infections, were also recorded. We analysed 139 patients with STEMI from three separate trials: VCUART (N = 10), VCUART2 (N = 30), and VCUART3 (N = 99). Of these, 84 (60%) patients were randomized to anakinra and 55 (40%) to placebo. Treatment with anakinra significantly reduced the incidence of all-cause death or new-onset HF (7 [8.2%] vs. 16 [29.1%], log-rank P = 0.002) and of all-cause death or HF hospitalization (0 [0] vs. 5 [9.1%], log-rank P = 0.007). Patients treated with anakinra had significantly higher injection site reactions (19 [22.6%] vs. 3 [5.5%], P = 0.016) without a significant difference in the incidence of serious infections (11 [13.1%] vs. 7 [12.7%], P = 0.435). Treatment with anakinra significantly reduced the area under the curve for high-sensitivity C-reactive protein between baseline and 14 days (75.48 [41.7-147.47] vs. 222.82 [117.22-399.28] mg day/L, P < 0.001).

Conclusion: IL-1 blockade with anakinra for 14 days in patients with STEMI reduces the incidence of new-onset HF or hospitalization for HF at 1 year following STEMI.

Keywords: Anakinra; Heart failure; Inflammation; Interleukin-1; STEMI.

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Figures

Figure 1
Figure 1
Kaplan–Meier curves for the incidence of the composite of all-cause death and new-onset heart failure and for the composite of all-cause death and heart failure hospitalizations, with a comparison between groups by log-rank test.
Figure 2
Figure 2
Kaplan–Meier curves for the incidence of the composite of new-onset heart failure or death according to treatment (placebo or anakinra) stratified by left ventricular ejection fraction (above or below the median), with a comparison between groups by log-rank test.
Figure 3
Figure 3
Effects of anakinra on high-sensitivity C-reactive protein. Anakinra (combined arms, n = 67) significantly reduced the area under the curve for high-sensitivity C-reactive protein at 14 days (shaded areas) compared to placebo (n = 48). Data are presented as median and interquartile range.
See this image and copyright information in PMC

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