The Effects of Anakinra on Cardiorespiratory Fitness in Heart Failure Stratified by Age in Phase II Clinical Trials

Cardiorespiratory fitness (CRF) in heart failure (HF) declines with age. Interleukin-1 is a proinflammatory cytokine involved in aging and HF. We aimed to determine the changes in CRF before and after treatment with anakinra, recombinant interleukin-1 receptor antagonist, in patients with HF stratified according to age younger and older than 60 years in phase II clinical trials. We analyzed data from 73 patients [37 (51%) female], 49 (67%) patients <60 years and 24 patients (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 (VO 2peak ) and high-sensitivity C-reactive protein (hsCRP). When compared with older patients, younger patients had higher baseline peak VO 2 [15.2 (12.4-17.7) vs. 12.4 (10.3-14.3) mL·kg -1 ·minute -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 VO 2peak [<60 years: +0.5 (-0.9 to 2.5) mL·kg -1 ·minute -1 ; P = 0.036; ≥60 years: +1.1 (0.2-2.3) mL·kg -1 ·minute -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 than younger patients despite similar levels of systemic inflammation, and they seem to have a similar improvement in CRF after 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.