Abstract 14792: The Effect of Interleukin-1 Receptor Antagonist Therapy on Markers of Inflammation in Non-ST Elevation Acute Coronary Syndromes: The MRC-ILA Heart Study
Objective: To investigate the effects of interleukin-1 receptor antagonist (IL-1ra, Anakinra, Amgen, USA) on high sensitivity c-reactive protein (hsCRP) in patients presenting with non-ST elevation ACS (NSTE-ACS).
Background: Acute coronary syndromes (ACS) are driven by inflammatory mechanisms. Interleukin-1 is an inflammatory cytokine with roles in atherosclerosis and response to vessel wall injury. We hypothesised that interleukin-1 inhibition would reduce the inflammatory response at the time of ACS.
Method: The present study is a phase II, double-blinded, randomized, placebo-controlled, study conducted in 5 UK centres. 182 patients with NSTE-ACS were allocated to once daily, subcutaneous injection of IL-1ra or placebo for 14 days.
Results: Baseline characteristics were well matched. Treatment compliance was 85% at seven days and 30 day mortality was 4%. The primary endpoint of geometric mean area under the curve for hsCRP was 21.98 mg.day/L (95%CI 16.31-29.64) in the IL-1ra group and 43.5mg.day/L (31.15-60.75) in the placebo group (geometric mean ratio=0.51 mg/L; 95%CI 0.32-0.79; p=0.0028). IL-6 levels at day 14 were lower in the treatment group (p=0.02). At 30 days hsCRP levels were higher in the IL-1ra group 3.50 mg/L (2.65-4.62) than the placebo group 2.21mg/L (1.67-2.92, p=0.022).
Conclusions: IL-1ra suppressed hsCRP over the first seven and 14 days following NSTE-ACS. The rise in CRP levels at day 30, following discontinuation of IL-1ra treatment, indicate that large-scale trials and studies of longer duration are required to assess impact on clinical outcomes.
- © 2013 by American Heart Association, Inc.