IL-1 Blockade in Patients With Heart Failure With Preserved Ejection Fraction

Circ Heart Fail. 2018 Aug;11(8):e005036. doi: 10.1161/CIRCHEARTFAILURE.118.005036.

Abstract

Background Enhanced inflammation may lead to exercise intolerance in heart failure with preserved ejection fraction. The aim of the current study was to determine whether IL (interleukin)-1 blockade with anakinra improved cardiorespiratory fitness in heart failure with preserved ejection fraction. Methods and Results Thirty-one patients with heart failure with preserved ejection fraction and CRP (C-reactive protein) >2 mg/L were randomized to anakinra (100 mg subcutaneously daily, N=21) or placebo (N=10) for 12 weeks. We measured peak oxygen consumption (Vo2), ventilatory efficiency (VE/Vco2 slope), and high-sensitivity CRP and NT-proBNP (N-terminal pro-B-type natriuretic peptide) at 4, 12, and 24 weeks. Twenty-eight patients completed ≥2 visits, 18 women (64%), 27 (96%) obese. There were no differences in peak Vo2 or VE/Vco2 slope between groups at baseline. Peak Vo2 was not changed after 12 weeks of anakinra (from 13.6 [11.8-18.0] to 14.2 [11.2-18.5] mL·kg-1·min-1, P=0.89), or placebo (14.9 [11.7-17.2] to 15.0 [13.8-16.9] mL·kg-1·min-1, P=0.40), without significant between-group differences in changes at 12 weeks (-0.4 [95% CI, -2.2 to +1.4], P=0.64). VE/Vco2 slope was also unchanged with anakinra (from 28.3 [27.2-33.0] to 30.5 [26.3-32.8], P=0.97) or placebo (from 31.6 [27.3-36.9] to 31.2 [27.8-33.4], P=0.78), without significant between-group differences in changes at 12 weeks (+1.2 [95% CI, -1.8 to +4.3], P=0.97). Within the anakinra-treated patients, high-sensitivity CRP and NT-proBNP levels were lower at 4 weeks compared with baseline ( P=0.026 and P=0.022 versus placebo [between-group analysis], respectively). Conclusions Treatment with anakinra for 12 weeks failed to improve peak Vo2 and VE/Vco2 slope in a group of obese heart failure with preserved ejection fraction patients. The favorable trends in high-sensitivity CRP and NT-proBNP with anakinra deserve exploration in future studies. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02173548.

Keywords: cardiorespiratory fitness; exercise test; heart failure; inflammation; interleukin-1; natriuretic peptides; oxygen consumption.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • C-Reactive Protein / metabolism
  • Cardiorespiratory Fitness*
  • Double-Blind Method
  • Echocardiography, Doppler
  • Exercise Test
  • Exercise Tolerance / drug effects*
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / immunology
  • Heart Failure / physiopathology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / adverse effects
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / immunology
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Oxygen Consumption / drug effects
  • Peptide Fragments / blood
  • Quality of Life
  • Recovery of Function
  • Stroke Volume*
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome
  • Ventricular Function, Left*

Substances

  • Anti-Inflammatory Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • C-Reactive Protein

Associated data

  • ClinicalTrials.gov/NCT02173548