Glatiramer acetate attenuates the cytokine surge associated with acute decompensated heart failure

BACKGROUND: Acute decompensated heart failure (ADHF) is characterized by a systemic inflammatory response with elevated circulating cytokines that correlate with adverse outcomes. Glatiramer acetate (GA), an established immunomodulatory agent, exerts broad effects on innate and adaptive immunity and has demonstrated cardioprotective properties in preclinical models. We hypothesized that GA could reduce the cytokine surge associated with ADHF. METHODS: We conducted a small, investigator-initiated, hypothesis-generating randomized clinical trial to evaluate the effects of GA on inflammatory cytokines in patients with ADHF and reduced ejection fraction. Patients were randomized 1:1 to standard care or an add-on treatment with GA. Circulating cytokines were measured using multiplex ELISA assays at baseline, day 2, and day 14. Secondary outcomes included changes in NT-proBNP and troponin. RESULTS: Fourteen patients were enrolled. GA therapy was associated with a broad attenuation of the cytokine response, with a significant reduction in IL-6 levels compared with standard care (adjusted p = 0.01). Analysis of normalized data demonstrated a marked blunting of the cytokine surge in the GA group at days 2 and 14 (pooled log2 fold-change -5.2 vs. +7.3, p < 0.0001). GA treatment was also associated with a reduction in NT-proBNP levels at both time points, whereas troponin levels were unchanged. No treatment-related adverse events were observed. CONCLUSIONS: In this proof-of-concept study, GA was associated with attenuation of the inflammatory cytokine surge and reduction in NT-proBNP levels in ADHF. These findings support further evaluation of GA in larger trials.