Effect of Interleukin-1 Blockade on Left Ventricular Systolic Performance and Work: A Post Hoc Pooled Analysis of 2 Clinical Trials

J Cardiovasc Pharmacol. 2018 Jul;72(1):68-70. doi: 10.1097/FJC.0000000000000591.

Abstract

Background: Interleukin-1 (IL-1) blockade seems to improve anaerobic exercise in patients with systolic heart failure through improved left ventricular (LV) systolic performance. However, it is unclear whether IL-1 blockade affects LV systolic performance.

Methods: We pooled data from 2 clinical trials of patients with systolic heart failure who were randomized to IL-1 blockade or placebo. We estimated changes in LV systolic performance (LV ejection fraction [LVEF] and end-systolic elastance [LVEes]) and pressure-volume area (PVA), a surrogate of oxygen consumption, after 14 days of treatment.

Results: LVEF increased from 30% (24%-38%) to 36% (29%-43%) between baseline and day 14 only in anakinra-treated patients (P = 0.03 for within-group change and P = 0.02 for between-group change compared with placebo). LVEes increased from 1.0 mm Hg/mL (0.7-1.5) to 1.3 mm Hg/mL (0.8-1.6) in anakinra-treated patients between baseline and day 14 but not in placebo-treated patients (P = 0.03 for within-group change and P = 0.08 for between-group change). A change in PVA between baseline and 14 days was not detected in either anakinra or placebo patients.

Conclusions: In this post hoc analysis, LVEes and LVEF increased significantly in patients treated with an IL-1 blocker but not in placebo-treated patients. An effect of IL-1 blockade on calculated PVA was not detected.

MeSH terms

  • Cardiotonic Agents / adverse effects
  • Cardiotonic Agents / therapeutic use*
  • Heart Failure, Systolic / diagnosis
  • Heart Failure, Systolic / drug therapy*
  • Heart Failure, Systolic / metabolism
  • Heart Failure, Systolic / physiopathology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / adverse effects
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / metabolism
  • Randomized Controlled Trials as Topic
  • Recovery of Function
  • Signal Transduction / drug effects
  • Stroke Volume / drug effects*
  • Time Factors
  • Treatment Outcome
  • Ventricular Dysfunction, Left / diagnosis
  • Ventricular Dysfunction, Left / drug therapy*
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left / drug effects*

Substances

  • Cardiotonic Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1