Interleukin‐1 blockade in heart failure: an on‐treatment and off‐treatment cardiorespiratory fitness analysis

AIMS: Interleukin‐1 (IL‐1) blockade may improve exercise capacity in patients with heart failure (HF) patients. The extent of the improvement and its persistence beyond discontinuation of IL‐1 blockade is unknown. METHODS AND RESULTS: The primary objective was to determine changes in cardiorespiratory fitness and cardiac function on‐treatment with IL‐1 blocker, anakinra, and off‐treatment, after treatment cessation. We performed cardiopulmonary exercise testing, Doppler echocardiography, and biomarkers in 73 patients with HF, 37 (51%) females, 52 (71%) Black–African–American, before and after treatment with anakinra 100 mg daily. In a subset of 46 patients, testing was also repeated after treatment cessation. Quality of life was assessed in each patient using standardized questionnaires. Data are presented as median and interquartile range. Treatment with anakinra for 4 [2–12] weeks was associated with a significant improvement in high‐sensitivity C‐reactive protein (from 6.2 [3.3–15.4] to 1.4 [0.8–3.4] mg/L, P < 0.001), peak oxygen consumption (VO(2peak), from 13.9 [11.6–16.6] to 15.2 [12.9–17.4] mL/kg/min, P < 0.001). Ventilatory efficiency, exercise time, Doppler‐derived signs and biomarkers of elevated intracardiac pressures, and quality‐of‐life measures also improved with anakinra. In the 46 patients in whom off‐treatment data were available 12 [4–12] weeks later, many of the favourable changes seen with anakinra were largely reversed (from 1.5 [1.0–3.4] to 5.9 [1.8–13.1], P = 0.001 for C‐reactive protein, and from 16.2 [14.0–18.4] to 14.9 [11.5–17.8] mL/kg/min, P = 0.017, for VO(2peak)). CONCLUSIONS: These data validate IL‐1 as an active and dynamic modulator of cardiac function and cardiorespiratory fitness in HF.