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

Eur Heart J Cardiovasc Pharmacother. 2022 Aug 11;8(5):503-510. doi: 10.1093/ehjcvp/pvab075.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • C-Reactive Protein / metabolism
  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Interleukin-1
  • Randomized Controlled Trials as Topic
  • ST Elevation Myocardial Infarction* / complications
  • ST Elevation Myocardial Infarction* / diagnosis
  • ST Elevation Myocardial Infarction* / drug therapy

Substances

  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • C-Reactive Protein