Anakinra treatment for 14 days significantly improved median peak oxygen consumption from 12.3 to 15.1 mL/kg/min in patients with systolic heart failure and elevated inflammatory signaling.
Does anakinra improve cardiopulmonary exercise performance in patients with systolic heart failure and elevated inflammatory signaling?
Tasa de eventos absoluta: 15.1% vs 12.3%
valor p: p=0.016
BACKGROUND: Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and poor exercise tolerance. Enhanced inflammation is associated with worsening outcomes in HF patients and may play a direct role in disease progression. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that becomes chronically elevated in HF and exerts putative negative inotropic effects. METHODS AND RESULTS: We developed a model of IL-1β-induced left ventricular (LV) dysfunction in healthy mice that exhibited a 32% reduction in LV fractional shortening (P<0.001) and a 76% reduction in isoproterenol response (P<0.01) at 4 hours following a single dose of IL-1β 3 mcg/kg. This phenotype was reproducible in mice injected with plasma from HF patients and fully preventable by pretreatment with IL-1 receptor antagonist (anakinra). This led to the design and conduct of a pilot clinical to test the effect of anakinra on cardiopulmonary exercise performance in patients with HF and evidence of elevated inflammatory signaling (n = 7). The median peak oxygen consumption (VO(2)) improved from 12.3 10.0, 15.2 to 15.1 13.7, 19.3 mL · kg(-1) · min(-1) (P = 0.016 vs. baseline) and median ventilator efficiency (V(E)/VCO(2) slope) improved from 28.1 22.8, 31.7 to 24.9 22.9, 28.3 (P = 0.031 vs. baseline). CONCLUSIONS: These findings suggest that IL-1β activity contributes to poor exercise tolerance in patients with systolic HF and identifies IL-1β blockade as a novel strategy for pharmacologic intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01300650.
Tassell et al. (Fri,) conducted a other in Systolic Heart Failure (n=7). Anakinra vs. Baseline was evaluated on Peak oxygen consumption (VO2) (p=0.016). Anakinra treatment for 14 days significantly improved median peak oxygen consumption from 12.3 to 15.1 mL/kg/min in patients with systolic heart failure and elevated inflammatory signaling.