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 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; 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. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01950299.

Keywords: ST‐segment–elevation myocardial infarction; acute myocardial infarction; heart failure; interleukin‐1.

Figure 1

Enrollment, randomization, and follow‐up. AUC indicates area under the curve; CKD, chronic kidney disease; hsCRP, high‐sensitivity C‐reactive protein; HF, heart failure; PCI, percutaneous coronary intervention.

Figure 2

Effects of anakinra on hsCRP (high‐sensitivity C‐reactive protein). Anakinra, once daily or twice daily, significantly reduced the area under the curve for hsCRP at 14 days (shaded areas) (P<0.001 for each anakinra group vs placebo, and P<0.001 for anakinra groups combined vs placebo). We found no significant difference between the once‐daily and twice‐daily anakinra regimens (P=0.41). Data are presented as median and interquartile range.

Figure 3

Effects of anakinra on heart failure clinical events. Anakinra‐treated patients had a significantly lower in incidence of heart failure related clinical events than placebo (Log‐rank Mantel‐Cox test). Left, a composite end point of new onset heart failure or death. Middle, a composite end point of hospitalization for heart failure or death. Right, a composite of ischemic events (death, recurrent AMI, or urgent revascularization).