Interleukin-1 Blockade in Patients With ST-Segment Elevation Myocardial Infarction Across the Spectrum of Coronary Artery Disease Complexity

J Cardiovasc Pharmacol. 2025 Mar 1;85(3):200-210. doi: 10.1097/FJC.0000000000001652.

Abstract

Patients with ST-segment elevation myocardial infarction (STEMI) and complex coronary artery disease (CAD) face a poor prognosis, including increased heart failure (HF) risk. Phase 2 clinical trials of anakinra have shown inhibition of the acute inflammatory response and prevention of HF after STEMI, but data on its effects based on CAD complexity are lacking. We performed a pooled secondary analysis of 139 patients with STEMI. The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), SYNTAX II, and Gensini scores were calculated, and patients were divided into 2 groups below and above the median. We evaluated the effect of anakinra on the area-under-the-curve of high-sensitivity C-reactive protein (hsCRP-AUC) at 14 days, and the composite endpoint of new-onset HF, HF hospitalization, or all-cause death at 1-year follow-up using Kaplan-Meier survival curves, Cox regression analysis for hazard ratios (HRs), and tested interactions between subgroups. All 3 CAD complexity scores (SYNTAX, SYNTAX II, and Gensini) were associated with an increased risk of adverse events (HR 1.02-1.06, all P-values ≤0.025). We found no statistically significant interactions between CAD extent, measured as single-vessel or multivessel CAD, SYNTAX score ≤9 or >9, SYNTAX II score ≤24 or >24, Gensini score ≤32 or >32, and treatment effect of anakinra on hsCRP-AUC or the composite clinical endpoint (all P - values for interaction >0.05). In conclusion, among patients with STEMI, IL-1 blockade with anakinra significantly attenuated the acute inflammatory response and reduced the risk of HF-related events regardless of the spectrum of CAD complexity.

Trial registration: ClinicalTrials.gov NCT00789724.

MeSH terms

  • Aged
  • Anti-Inflammatory Agents* / adverse effects
  • Anti-Inflammatory Agents* / therapeutic use
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Coronary Artery Disease* / diagnostic imaging
  • Coronary Artery Disease* / drug therapy
  • Coronary Artery Disease* / mortality
  • Coronary Artery Disease* / therapy
  • Female
  • Heart Failure / etiology
  • Heart Failure / mortality
  • Heart Failure / prevention & control
  • Humans
  • Interleukin 1 Receptor Antagonist Protein* / adverse effects
  • Interleukin 1 Receptor Antagonist Protein* / therapeutic use
  • Interleukin-1* / antagonists & inhibitors
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / mortality
  • Risk Assessment
  • Risk Factors
  • ST Elevation Myocardial Infarction* / diagnostic imaging
  • ST Elevation Myocardial Infarction* / drug therapy
  • ST Elevation Myocardial Infarction* / mortality
  • ST Elevation Myocardial Infarction* / therapy
  • Time Factors
  • Treatment Outcome

Substances

  • Interleukin 1 Receptor Antagonist Protein
  • C-Reactive Protein
  • Biomarkers
  • Interleukin-1
  • Anti-Inflammatory Agents

Associated data

  • ClinicalTrials.gov/NCT00789724