Abstract 12116: Effects of Interleukin-1 Blockade With Anakinra on Peak Oxygen Consumption in Patients With Heart Failure an Analysis of On-Treatment and Off-Treatment Assessments

Abstract

Introduction: Interleukin-1 (IL-1) blockade may improve exercise capacity in the subset of heart failure (HF) patient with high inflammation. Accordingly, modulating systemic inflammation with IL-1 inhibition could result in physiologic adaptations that have a beneficial effect on exercise capacity in this population. Hypothesis: Primary objective of the study was to determine changes in peak oxygen consumption (VO2) on-treatment with anakinra, an IL-1 blocker, and after treatment cessation. Methods: Cardiopulmonary exercise testing (CPET) was performed in 52 patients with HF at baseline, during daily treatment and after suspension of treatment with 100 mg anakinra. High-sensitivity C-reactive protein (CRP) was measured at the time of each CPET. Data are presented as median and interquartile range or number and percentage. Results: The cohort included twenty-six (50%) females, 36 (69%) self-identified as Black/African-American, 55 [52-62] years. Left ventricular ejection fraction (LVEF) was 43% [34-60%], CRP was 7.1 [3.7-15.8] mg/L and peak VO2 was 14.5 [12.6-17.4] ml•kg-1•min-1. Treatment duration was 4 [2-12] weeks, while time between treatment discontinuation and off-treatment CPET was 12 [6-12] weeks. Treatment with anakinra significantly reduced CRP (7.1 [3.7-15.8] to 1.5 [1.0-3.8] mg/L, p<0.001) and improved peak VO2 (14.5 [12.6-17.4] ml•kg-1•min-1to 16.0 [14.0-18.6] ml•kg-1•min-1, p=0.011-Figures A and B, respectively). CRP significantly increased to 3.8 [1.4-10.7] mg/L, p=0.007, and peak VO2 significantly decreased to 15.5 [12-17.8] ml•kg-1•min-1 (p= 0.004) after anakinra suspension. Conclusions: IL-1 blockade with anakinra is associated with a reduction in systemic inflammation (CRP levels) and in an improvement in exercise capacity (i.e., peak VO2) among patients with HF during treatment. These data validate IL-1 blockade as a mediator of exercise capacity in HF; however long-term effects require further investigation.