Benjamin W. Van Tassell, Michele Golino, Justin M. Canada, Roshanak Markley, Hayley Billingsley, Marco Giuseppe Del Buono, Azita Talasaz, Georgia Thomas, Juan Guido Chiabrando, George F. Wohlford, Virginia Dickson, Dinesh Kadariya, Juan Ignacio Damonte, Ai‐Chen Ho, Yub Raj Sedhai, Emily Kontos, Alessandra Vecchié, Joshua D. West, Giuliana Corna, Horacio Medina de Chazal, Sebastian Piñel, Edoardo Bressi, Andrew Barron, Megan Dell, James Mbualungu, Francesco Moroni, Jeremy Turlington, Emily Federmann, Cory R. Trankle, Salvatore Carbone, Ross Anthony Arena, Antonio Abbate
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.