Abstract
BACKGROUND: 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 (VO(2)) in patients with recently decompensated HFrEF. METHODS: 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 VO(2) change at 24 weeks. Data are presented as median (Q1, Q3) or number (%). RESULTS: Of the 102 patients, 84 had primary end point data available (57 treated with anakinra and 27 with placebo). Peak VO(2) 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 VO(2) 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). CONCLUSIONS: Patients with recently decompensated HFrEF treated with maximally tolerated medical therapy had a significant improvement in CRP and peak VO(2). The addition of anakinra had a modest effect on CRP levels and no significant effect on peak VO(2) or other clinically relevant secondary end points. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797001.