Anakinra reduced CRP by 76% vs 48% with placebo (P=0.050) but did not significantly improve peak VO2 in recently decompensated HFrEF patients.
Does anakinra improve peak VO2 in adult patients with recently decompensated HFrEF and elevated CRP?
In patients with recently decompensated HFrEF, the addition of anakinra to maximally tolerated medical therapy did not significantly improve peak VO2 compared to placebo.
Absolute Event Rate: 0% vs 0%
Abstract Background Interleukin-1 (IL-1) is an inflammatory cytokine involved in heart failure with reduced ejection fraction (HFrEF). Purpose We sought to determine whether anakinra, an IL-1 blocker, can favor the resolution of systemic inflammation (C-reactive protein CRP) and improve peak oxygen consumption (VO2) in HFrEF. Methods We conducted a single-center, randomized, trial with a 2:1 allocation to anakinra 100 mg daily or placebo for 24 weeks in 102 adult patients within 2 weeks of hospitalization for HFrEF and with CRP ≥2 mg/L. Peak VO2 was measured using a cardiopulmonary exercise test at 0, 6, 12 and 24 weeks. Medical therapy was intensified at each visit. The primary endpoint was the change in peak VO2 at the longest available follow-up. Data are presented as number (%) or median interquartile range. Results Of the 102, 84 patients had data available for the primary endpoint, 57 (68%) treated with anakinra and 27 (32%) with placebo, 28 (33%) female, 59 (70%) Black, 57.5 46.2-65.0 years of age. A significant reduction in CRP levels was seen in the entire cohort, with a -76% from -87% to -36% in anakinra-treated patients and -48% from -77% to +14% in the placebo group (P=0.050 between groups). Although peak VO2 in the entire cohort increased from 13.0 10.9-17.0 to 14.9 12.0-18.0 mL•Kg-1•min-1 (P0.001), there were no significant differences between anakinra and placebo (+1.5 and +1.2 mL•Kg-1•min-1, respectively, P=0.60). There were no unexpected treatment-related serious adverse events and no differences in HF events between groups. CRP2 mg/L was achieved in 44% patients, 47% in anakinra and 37% in placebo (P=0.37). Patients achieving CRP2 mg/L had a significantly greater increase in peak VO2 versus those with CRP≥2 mg/L (+2.6 vs +1.0 ml•Kg-1•min-1, P=0.007) and lower rates of HFrEF-related events (8% vs 26%, P=0.045). Conclusion Patients with recently decompensated HFrEF treated with maximally tolerated medical therapy have a significant improvement in CRP and peak VO2. The addition of anakinra has a modest effect on the CRP and no significant effects on peak VO2. Additional studies are warranted to determine whether a different strategy of anti-inflammatory therapy can further improve outcomes.
Tassell et al. (Sat,) reported a other. Anakinra reduced CRP by 76% vs 48% with placebo (P=0.050) but did not significantly improve peak VO2 in recently decompensated HFrEF patients.