Objectives: Patients with complex coronary artery disease (CAD) presenting with ST-segment elevation myocardial infarction (STEMI) face a poor prognosis, including an increased risk of developing heart failure (HF). Interleukin-1 (IL-1) blockade has emerged as a promising therapeutic strategy to inhibit the acute inflammatory response and prevent HF in patients with STEMI, but comprehensive data on its effects according to CAD complexity remain elusive. The aim of this analysis was to explore the effects of Anakinra, a recombinant IL-1 receptor antagonist, in patients with STEMI, based on the presence or absence of multivessel CAD at baseline angiography and according to CAD complexity stratification using the SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), SYNTAX II, and Gensini scores.

Methods and Results: We performed a pooled secondary analysis of 139 patients from three early phase randomized clinical trials comparing anakinra (N=84) versus placebo (N=55) in subjects with STEMI (VCUART studies). Multivessel CAD was defined as the presence of at least one angiographically significant stenosis (≥70% of the vessel diameter on visual estimation) and non-infarct-related (non-culprit) lesion, located in a vessel with a diameter of at least 2.5 mm that was not stented as part of the index culprit-lesion percutaneous coronary intervention. The SYNTAX, SYNTAX II and Gensini scores were calculated by two independent operators based on the index coronary angiogram and clinical parameters. Patients were divided into different subgroups, considering the median of the sample: SYNTAX score ≤9 or >9, SYNTAX II score ≤24 or >24 and Gensini score ≤32 or >32. We evaluated a composite of new-onset HF, HF hospitalization, or all-cause death at 1-year follow-up as primary efficacy analysis using Kaplan-Meier survival curves and Hazard Ratios (HR) with 95% Confidence Interval (CI) using Cox regression analysis. We included 139 patients with STEMI, 85 (61%) with single-vessel CAD and 54 (39%) with multi-vessel CAD. According to the spectrum of CAD complexity, 60 (43%) presented a SYNTAX score >9, 59 (42%) a SYNTAX II score >24 and 65 (47%) a Gensini score >32. At 1-year follow-up period, patients treated with anakinra showed a lower incidence of the primary composite outcome compared to placebo (7 of 84 [8%] vs 16 of 55 [29%], respectively; HR 0.28 [95% CI, 0.11-0.67], p=0.005). We found no statistically significant interactions between CAD complexity and allocation to anakinra or placebo: single-vessel vs multi-vessel CAD (HR 0.42 [95% CI, 0.15-1.23] p=0.11, and HR 0.10 [0.01-0.79] p=0.03, respectively; p for interaction= 0.20); SYNTAX score ≤9 vs >9 (HR 0.41 [95% CI, 0.11-1.45] p=0.17, and HR 0.22 [95% CI, 0.06-0.79] p=0.02, respectively; p for interaction= 0.54); SYNTAX II score ≤24 vs >24 (HR 0.41 [95% CI, 0.10-1.73] p=0.23, and HR 0.22 [95% CI, 0.06-0.79] p=0.02, respectively; p for interaction= 0.49); Gensini score ≤32 and >32 (HR 0.42 [95% CI, 0.10-1.75] p=0.23, and HR 0.22 [95% CI, 0.07-0.70] p=0.01, respectively; p for interaction= 0.54).

Conclusions: Among patients with STEMI, IL-1 blockade with anakinra significantly reduced the risk of new-onset HF, HF hospitalization, or all-cause death compared to placebo, without statistically significant differences across the number of vessels affected and the spectrum of CAD complexity.