Interleukin-1 Receptor Antagonist Levels in Patients With Heart Failure and Reduced Ejection Fraction Treated With Anakinra

Patients with heart failure and reduced ejection fraction (HFrEF) commonly show signs of systemic inflammation. Interleukin-1 (IL-1) is a proinflammatory cytokine, known to modulate cardiac function. We aimed to determine the effects of treatment with anakinra, a recombinant IL-1 receptor antagonist (IL-1Ra), on plasma IL-1Ra levels. We measured IL-1Ra levels at baseline and longest available follow-up to 24 weeks in 63 patients (44 men, 40 self-identified Black Americans) with recent hospitalization for HFrEF and systemic inflammation [C-reactive protein (CRP) levels >2 mg/L] who were assigned to anakinra [n = 42 (66.7%)] or placebo [n = 21 (33.3%)] as part of the REDHART2 clinical trial (NCT03797001). Cardiorespiratory fitness was measured as peak oxygen consumption (VO 2peak ). Baseline plasma IL-1Ra levels were 380 [290 to 1046] pg/mL. On-treatment IL-1Ra levels were significantly higher in the patients treated with anakinra versus placebo [3994 (3372 to 5000) pg/mL vs. 492 (304 to 1370) pg/mL, P < 0.001]. The longest available follow-up was 6 weeks in 10 patients (15.9%), 12 weeks in 12 patients (19%), and 24 weeks in 41 patients (65.1%). On-treatment IL-1Ra levels and interval change in IL-1Ra showed a modest inverse correlation with on-treatment CRP levels (R = -0.269, P = 0.033 and R=-0.355, P = 0.004, respectively) and no statistically significant correlations with VO 2peak values ( P > 0.05). Patients with recently decompensated HFrEF and systemic inflammation treated with recombinant IL-1Ra, anakinra, had a significant several-fold increase in plasma IL-1Ra levels. On-treatment IL-1Ra levels, however, showed only a modest correlation with CRP levels and not with VO 2peak.