Rikken Sem A O F, Gibson C Michael, Bahit M Cecilia, Duffy Danielle, Chi Gerald, Korjian Serge, Mohammadnia Niekbachsh, White Harvey, Anschuetz Gaya, Kingwell Bronwyn A, Ophuis Ton Oude, Nicolau Jose C, Lopes Renato D, Lewis Basil S, El Messaoudi Saloua, Vinereanu Dragos, Ten Berg Jurriën M, Goodman Shaun G, Bode Christoph, Steg P Gabriel, Libby Peter, Bainey Kevin R, van 't Hof Arnoud W J, Ridker Paul M, Mahaffey Kenneth W, Nicholls Stephen J, Mehran Roxana, Harrington Robert A, Cornel Jan H
Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands; Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands; Baim Institute for Clinical Research, Boston, Massachusetts, USA.
Baim Institute for Clinical Research, Boston, Massachusetts, USA; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
JACC Adv. 2025 Mar 29;4(5):101727. doi: 10.1016/j.jacadv.2025.101727.
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).
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.
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.
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 = 0.010) and among treatment, NLR, and LDL-C at 180 days (P = 0.029).
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.
AEGIS-II（缺血综合征中载脂蛋白A-I事件减少-II；NCT03473223）试验评估了CSL112（一种人血浆源性载脂蛋白A-I疗法）在急性心肌梗死（AMI）后降低心血管事件的效果。鉴于CSL112潜在的抗炎特性，我们进行了一项探索性的事后分析，以确定其疗效是否受全身炎症标志物基线中性粒细胞与淋巴细胞比值（NLR）和低密度脂蛋白胆固醇（LDL-C）的影响。
本研究旨在调查基线NLR与心血管事件之间的关联，并探讨NLR和LDL-C是否会改变CSL112在AMI后患者中的疗效。
共有18219名患有AMI、多支冠状动脉疾病及其他心血管危险因素的参与者被随机分为接受4次每周6克CSL112或安慰剂输注。主要终点是心血管死亡、心肌梗死或中风的复合终点（主要不良心血管事件 [MACE]）。Cox比例风险模型通过二分法基线NLR（>中位数 vs ≤中位数）评估风险。评估了治疗与NLR以及LDL-C（≥100 vs <100 mg/dL）之间的相互作用。
在15966名参与者中，基线NLR>中位数（>3.3）的参与者在90天时发生MACE的风险显著更高（HR：1.40；95%CI：1.21-1.63），在180天和365天时持续存在。CSL112在NLR升高且LDL-C≥100 mg/dL的参与者中，在90天时降低了MACE（HR：0.63；95%CI：0.42-0.93），在180天和365天时持续受益。在治疗与NLR之间（P = 0.010）以及在180天时治疗、NLR和LDL-C之间观察到显著的相互作用（P = 0.029）。
基线NLR升高可预测AMI后患者的MACE，并且CSL112在NLR升高且LDL-C≥100 mg/dL的患者中显示出MACE的相关降低。
