Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome of exercise intolerance due to impaired myocardial relaxation and/or increased stiffness. Patient with HFpEF often show signs of chronic systemic inflammation and experimental studies show that interleukin-1 (IL-1), a key pro-inflammatory cytokine, impairs myocardial relaxation. The aim of the current study was to determine the effects of IL-1 blockade with anakinra on aerobic exercise capacity in patients with HFpEF and plasma C-reactive protein (CRP) >2 mg/l (reflecting increased IL-1 activity). Twelve patients were enrolled in a double-blind, randomized, placebo-controlled, cross-over trial and assigned 1:1 to receive one of the 2 treatments (anakinra 100 mg or placebo) for 14 days and then an additional 14 days of the alternate treatment (placebo or anakinra). Cardiopulmonary exercise testing (CPX) was performed at baseline, after the first 14 days and after the second 14 days. Placebo-corrected interval change in peak oxygen consumption (VO2) was chosen as primary endpoint. All 12 patients enrolled in the study and receiving treatment completed both phases, and experienced no major adverse events. Anakinra led to a statistically significant improvement in peak VO2 (+1.2 ml•kg−1•min−1, P=0.009), and a significant reduction in plasma CRP levels (−74%, P=0.006). The reduction in CRP levels was correlated with the improvement in peak VO2 (R=-0.60, P=0.002). Three patients (25%) had mild and self-limiting injection site reactions. In conclusion, IL-1 blockade with anakinra for 14 days significantly quenches the systemic inflammatory response and improves aerobic exercise capacity in patients with HFpEF and elevated plasma CRP levels.

IL-1 blockade therapies using rhIL-1Ra prior the onset of AMI protects the myocardium and preserves cardiac function.

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