Hogwood AC; Robert M. Berne Cardiovascular Research Center, and Division of Cardiology, University of Virginia, Charlottesville, Virginia, United States.
Golino M; Moroni F; Canada JM; Del Buono MG; Arena R;Van Tassell B; Abbate A;

Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 2025 Sep 09.
Date of Electronic Publication: 2025 Sep 09.

Competing Interests: Dr. Abbate has served as consultant to Kiniksa, Monte Rosa Therapeutics, and Novo Nordisk.
Cardiorespiratory fitness (CRF) in heart failure (HF) declines with age. Interleukin-1 (IL-1) is a pro-inflammatory cytokine involved in aging and HF. We aimed to determine the changes in CRF before and after treatment with anakinra, recombinant IL-1 receptor antagonist, in patients with HF stratified according to age below and above 60 years in phase II clinical trials. We analyzed data from 73 patients (37 [51%] female), 49 (67%) patients ˂60 years and 24 (33%) ≥60 years. All patients received anakinra 100 mg subcutaneously daily for a median of 4 (interquartile range from 2 to 12) weeks. We measured peak oxygen consumption (VO2peak) and high-sensitivity C-reactive protein (hsCRP). When compared with older patients, younger patients had higher baseline peak VO2 (15.2 [12.4-17.7] vs. 12.4 [10.3-14.3] mL·kg-1·min-1, p=0.001), yet no significant differences in hsCRP (6.6 [3.6-16.6] vs. 5.2 [2.7-11.2] mg/L, p=0.18). In both groups, anakinra decreased hsCRP (<60 years: -3.6 [-8.1 to -1.9] mg/L; p<0.001; ≥60 years: -2.7 [-9.0 to -1.4] mg/L; p<0.001) and increased peak VO2peak (<60 years: +0.5 [-0.9 – 2.5] mL·kg-1·min-1; p=0.036; ≥60 years: +1.1 [0.2 – 2.3] mL·kg-1·min-1; p<0.001). No significant differences in changes across time were observed between the age groups. Older patients with HF have a greater baseline impairment in CRF compared to younger patients despite similar levels of systemic inflammation, and they appear to have a similar improvement in CRF following treatment with anakinra. The lack of an active control group (placebo) is a significant limitation and additional studies are needed to validate and expand these findings assessing clinical outcomes.