Effect of IL-1 Blockade With Anakinra on Heart Failure Outcomes in Patients With Anterior Versus Nonanterior ST Elevation Myocardial Infarction

J Cardiovasc Pharmacol. 2022 Jun 1;79(6):774-780. doi: 10.1097/FJC.0000000000001240.

Abstract

Patients with ST elevation myocardial infarction (STEMI) are at risk of future heart failure (HF), particularly those with anterior STEMI. Interleukin-1 (IL-1) is a key mediator of the inflammatory response, and its blockade has emerged as a potential therapeutic strategy to prevent HF events. The aim of this analysis was to explore the effects of anakinra, an IL-1 receptor antagonist, on HF outcomes based on anterior versus nonanterior location STEMI and to explore whether this effect is mediated through the amelioration of left ventricular systolic function and cardiac remodeling. We pooled data from 3 early phase randomized clinical trials. The primary end point was a composite of all-cause death and new-onset HF at 1-year follow-up. The left anterior descending coronary artery as culprit vessel was used to identify anterior STEMI. We included 139 patients, 47 (34%) with anterior STEMI and 92 (66%) with nonanterior STEMI. Anakinra significantly reduced the combined end point of death or new-onset HF in patients with anterior STEMI [4 (13%) vs. 7 (42%), log-rank P value = 0.049] and in patients with nonanterior STEMI [3 (6%) vs. 9 (24%), log-rank P value = 0.014]. We found no significant differences comparing anakinra versus placebo in interval changes in left ventricular ejection fraction and volumes in anterior and nonanterior STEMI. In conclusion, anakinra is associated with a reduction of HF events in patients with STEMI, irrespective of anterior or nonanterior location, or of changes in left ventricular ejection fraction or cardiac remodeling.

Trial registration: ClinicalTrials.gov NCT00789724.

Publication types

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

MeSH terms

  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Heart Failure* / etiology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / adverse effects
  • Interleukin-1
  • Percutaneous Coronary Intervention* / adverse effects
  • ST Elevation Myocardial Infarction* / diagnostic imaging
  • ST Elevation Myocardial Infarction* / drug therapy
  • Stroke Volume
  • Ventricular Function, Left
  • Ventricular Remodeling

Substances

  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1

Associated data

  • ClinicalTrials.gov/NCT00789724