Interleukin‐1 Blockade Inhibits the Acute Inflammatory Response in Patients With ST‐Segment–Elevation Myocardial Infarction

Background ST-segment-elevation myocardial infarction is associated with an intense acute inflammatory response and risk of heart failure. We tested whether interleukin-1 blockade with anakinra significantly reduced the area under the curve for hsCRP (high sensitivity C-reactive protein) levels during the first 14 days in patients with ST-segment-elevation myocardial infarction (VCUART3 Virginia Commonwealth University Anakinra Remodeling Trial 3). Methods and Results We conducted a randomized, placebo-controlled, double-blind, clinical trial in 99 patients with ST-segment-elevation myocardial infarction in which patients were assigned to 2 weeks treatment with anakinra once daily (N=33), anakinra twice daily (N=31), or placebo (N=35). hsCRP area under the curve was significantly lower in patients receiving anakinra versus placebo (median, 67 interquartile range, 39-120 versus 214 interquartile range, 131-394 mg·day/L; PP=0.21) or left ventricular ejection fraction (median, 3.9% interquartile range, -1.6% to 10.2% versus 2.7% interquartile range, -1.8% to 9.3%; P=0.61) at 12 months. The incidence of death or new-onset heart failure or of death and hospitalization for heart failure was significantly lower with anakinra versus placebo (9.4% versus 25.7% P=0.046 and 0% versus 11.4% P=0.011, respectively), without difference between the anakinra arms. The incidence of serious infection was not different between anakinra and placebo groups (14% versus 14%; P=0.98). Injection site reactions occurred more frequently in patients receiving anakinra (22%) versus placebo (3%; P=0.016). Conclusions In patients presenting with ST-segment-elevation myocardial infarction, interleukin-1 blockade with anakinra significantly reduces the systemic inflammatory response compared with placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01950299.