Resolution of Systemic Inflammation in Patients With Recently Decompensated Heart Failure With Reduced Ejection...

Decompensated heart failure with reduced ejection fraction (HFrEF) is associated with systemic inflammation that predicts unfavorable outcomes. We aimed to determine whether anakinra, an IL-1 (interleukin-1) blocker, favors inflammation resolution (CRP [C-reactive protein]) and improves peak oxygen consumption (VO₂) in patients with recently decompensated HFrEF.

We randomized 102 adult patients recently hospitalized for HFrEF and CRP ≥2 mg/L (2:1) to receive anakinra 100 mg subcutaneously daily (n=68) or placebo for 24 weeks (n=34). The primary end point was the peak VO₂ change at 24 weeks. Data are presented as median (Q1, Q3) or number (%).

Of the 102 patients, 84 had primary end point data available (57 treated with anakinra and 27 with placebo). Peak VO₂ increased from 13.0 (10.9, 17.0) to 14.9 (12.0, 18.0) mL·kg⁻¹·min⁻¹ (P<0.001) in the entire cohort, without significant differences between anakinra and placebo (+1.5 [-0.2, +3.4] and +1.2 [+0.5, +3.9] mL·kg⁻¹·min⁻¹, respectively; P=0.40; median difference +0.30 mL·kg⁻¹·min⁻¹ [95% CI from -1.70 to +0.90]). A significant reduction in CRP levels was seen, with a -76% (-87%, -36%) in anakinra-treated patients and -48% (-77%, +14%) in the placebo group (P=0.050 between groups). There were no unexpected treatment-related serious adverse events, and no differences in HFrEF events between groups. CRP<2 mg/L was achieved in 47% and 37% of the anakinra and placebo groups, respectively (P=0.48). Patients achieving CRP<2 mg/L had a significantly greater increase in peak VO₂ versus those with CRP≥2 mg/L (+2.6 [+0.7, +4.6] and +1.0 [-0.3, +1.9] mL·kg⁻¹·min⁻¹; P=0.007) and lower rates of HFrEF-related events (8% and 26%; P=0.045).

Patients with recently decompensated HFrEF treated with maximally tolerated medical therapy had a significant improvement in CRP and peak VO₂. The addition of anakinra had a modest effect on CRP levels and no significant effect on peak VO₂ or other clinically relevant secondary end points.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797001.