Anakinra reduced CRP levels by 76% compared to 48% in placebo, but had no significant impact on peak VO2 in patients with decompensated HFrEF.
Does anakinra improve peak VO2 at 24 weeks in adult patients recently hospitalized for HFrEF with CRP ≥2 mg/L?
In patients with recently decompensated HFrEF, the addition of anakinra to maximally tolerated medical therapy did not significantly improve peak VO2 compared to placebo, despite a modest reduction in CRP levels.
Absolute Event Rate: 0% vs 0%
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.
Tassell et al. (Tue,) reported a other. Anakinra reduced CRP levels by 76% compared to 48% in placebo, but had no significant impact on peak VO2 in patients with decompensated HFrEF.