Diabetes mellitus and response to IL-1 blockade with Anakinra after ST-elevation myocardial infarction: a pooled analysis of the VCU-ART studies

Abstract Background ST segment elevation myocardial infarction (STEMI) elicits an intense inflammatory response which is thought to contribute to subsequent maladaptive myocardial healing and remodeling, ultimately leading to heart failure (HF). The interleukin-1 (IL-1) blocker anakinra administered during the first 14 days after STEMI patients has been shown to effectively dampen the inflammatory response and reduce the incidence of HF events in pilot randomized controlled trials. Diabetes mellitus is a condition of enhanced systemic inflammation. Purpose To assess the role of diabetes mellitus as a modulating factor in respect to the efficacy of anakinra treatment during the first 14 days after STEMI. Methods We conducted a pooled analysis of three previous proof of principle trials on anakinra in STEMI. Diabetes mellitus was defined based on clinical history, use of glucose-lowering medications, or elevated hemoglobin A1c >6.5% at time of enrollment and further characterized as type I or type II based on the available clinical assessment. The area-under-the-curve for C reactive protein (AUC-CRP) at 14 days was used as a measure of the systemic inflammatory response during STEMI. The clinical endpoint was composite of death, hospitalizations for HF and urgent HF visits. Results The study population included 139 patients, of whom 39 (28%) had a diagnosis of diabetes mellitus at time of enrolment, all with type II. Median age was 56 [49-63] and 56 [49-63] years in patients with and without diabetes, respectively (p=0.652). There were 29 (21%) female and 52 (37%) Black-African American patients among those with diabetes compared to 29 (21%) female and 52 (37%) Black-African American patients in those without diabetes (p=0.69 and p=0.16, respectively). Treatment with anakinra (N=84) significantly dampened acute inflammation associated with STEMI in patients with diabetes (AUC-CRP 223 [117-399] vs 76 [42-148] mg•day/L, p<0.001) and in those without diabetes (AUC-CRP 223 [117-399] vs 76 [42-148] mg•day/L, p<0.001 – Figure 1). No statistically significant interaction between diabetes status and treatment with anakinra on outcomes was detected (pint=0.92): treatment with anakinra was associated with a hazard ratio [HR] 0.28 [0.09-0.84](p=0.02) in non-diabetic patients and HR 0.26 [0.11-1.32](p=0.10) in diabetic patients – Figure 2. Conclusion In this pooled analysis of the VCU-ART trials, the presence of type II diabetes mellitus showed no interaction with the efficacy of the treatment with anakinra early after STEMI in reducing the systemic inflammatory response or preventing new onset heart failure, hospitalization for HF or death.Figure 1.Figure 2