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

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.