Impact of Apolipoprotein A-I Infusions on Cardiovascular Events Post-MI by Neutrophil-Lymphocyte Ratio and LDL-Cholesterol Levels.

Overview

abstract

BACKGROUND: The AEGIS-II (ApoA-I Event Reducing in Ischemic Syndromes-II; NCT03473223) trial evaluated CSL112, a human plasma-derived apolipoprotein A-I therapy, for reducing cardiovascular events after acute myocardial infarction (AMI). Given CSL112's potential anti-inflammatory properties, we conducted an exploratory post hoc analysis to determine if its efficacy is influenced by baseline neutrophil-lymphocyte ratio (NLR), a marker of systemic inflammation, and low-density lipoprotein cholesterol (LDL-C). OBJECTIVES: The purpose of this study was to investigate the association of baseline NLR and cardiovascular events and explore whether NLR and LDL-C modify CSL112's efficacy in post-AMI patients. METHODS: A total of 18,219 participants with AMI, multivessel coronary artery disease, and additional cardiovascular risk factors were randomized to 4 weekly infusions of 6 g CSL112 or placebo. The primary endpoint was a composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]). Cox proportional hazards models evaluated risk by dichotomized baseline NLR (>median vs ≤median). Treatment interactions with NLR and LDL-C (≥100 vs <100 mg/dL) were assessed. RESULTS: Among 15,966 participants, those with baseline NLR >median (>3.3) had a significantly greater risk of MACE at 90 days (HR: 1.40; 95% CI: 1.21-1.63), persisting at 180 and 365 days. CSL112 reduced MACE at 90 days among participants with elevated NLR and LDL-C ≥100 mg/dL (HR: 0.63; 95% CI: 0.42-0.93), with sustained benefits at 180 and 365 days. Significant interactions were observed between treatment and NLR (P_interaction = 0.010) and among treatment, NLR, and LDL-C at 180 days (P_interaction = 0.029). CONCLUSIONS: Baseline elevated NLR predicts MACE in post-AMI patients, and CSL112 showed an associated reduction in MACE in patients with elevated NLR and LDL-C ≥100 mg/dL.