Abstract 4340531: Interleukin-1 Blockade in Patients With ST-Segment-Elevation Myocardial Infarction: a Pooled Analysis of Randomized Clinical Trials of Anakinra and Goflikicept

Abstract

Background: STEMI triggers an intense inflammatory response and Interleukin-1 (IL-1) is associated with adverse cardiovascular outcomes, including heart failure (HF). IL-1 blockade with anakinra or goflikicept is a promising therapeutic strategy to dampen inflammation during STEMI. Aim: To evaluate the effect of IL-1 blockade with anakinra and goflikicept on inflammation, left ventricular function, and clinical outcomes in STEMI patients. Methods: We conducted a patient-level analysis of four randomized, double-blind, phase II trials in STEMI patients treated with an IL-1 blocker (anakinra or goflikicept) or placebo. The primary endpoint was a composite of outpatient new-onset HF, hospitalization for HF, or death at 1 year. Secondary endpoints included each component of the primary endpoint, 14-day area-under-the-curve for C-reactive protein (AUC-CRP), NT-proBNP levels at 14 days and 1 year, and prevalence of left ventricular systolic dysfunction (LVEF<45%) at 1 year. Data are presented as n (%) or median (Q1-Q3). Groups were compared with the Mann–Whitney U or chi-square tests. Outcomes were analyzed with the log-rank test and Cox regression for hazard ratios (HR). Odds ratios (ORs) for LVEF <45% at 1 year were estimated using logistic regression. A p-value <0.05 was considered significant. Results: We studied 241 patients: 152 (63%) treated with an IL-1 blocker (84 anakinra, 68 goflikicept) and 89 (37%) with placebo. Median age was 57 [50–65] years, 184 (76%) were males and 184 (76%) White. IL-1 blockade significantly reduced the 1-year incidence of the composite outcome of new-onset HF, hospitalization for HF, or death (7.9% vs. 21.3%, log-rank p=0.004; HR 0.362, 95% CI [0.176–0.746], p=0.006), as well as hospitalization for HF or death (0.7% vs. 6.7%, log-rank p=0.008; HR 0.099, 95% CI [0.012–0.824], p=0.032)( Figures 1-2 ). The AUC-CRP at 14 days was lower with IL-1 blockers vs. placebo (90.0 [47.7–197.5] vs. 201.3 [112.9–362.4] mg*day/L, p<0.001). NT-proBNP levels were similar at 14 days or 1 year. Patients receiving IL-1 blockers had a significantly lower prevalence of LV systolic dysfunction (11.2% vs 22.2%, p=0.042; OR 0.442, 95% CI [0.198–0.984], p=0.046). Conclusions: Phase II trials of IL-1 inhibition with anakinra and goflikicept show inhibition of systemic inflammation, prevention of LV systolic dysfunction, and reduction of HF-related events at 1 year. Adequately powered phase III clinical trials are needed to validate and expand these findings.