Interleukin-1 blockade inhibits the acute inflammatory response in patients with st-segment–elevation myocardial infarction

Abstract

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 STsegment–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] mgday/L; P<0.001), without significant differences between the anakinra arms. No significant differences were found between anakinra and placebo groups in the interval changes in left ventricular end-systolic volume (median, 1.4 [interquartile range, 9.8 to 9.8] versus 3.9 [interquartile range, 15.4 to 1.4] mL; P=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.