Rationale, Design, and Baseline Clinical Characteristics of the Ziltivekimab Cardiovascular Outcomes Trial: Interleukin-6 Inhibition and Atherosclerotic Event Rate Reduction.

Patients with chronic kidney disease (CKD) commonly have plasma elevations of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hsCRP) and IL-6, and are at high risk for life-threatening atherosclerotic events as well as loss of kidney function and might therefore benefit from IL-6 inhibition.

慢性肾脏病（CKD）患者通常有炎症生物标志物的血浆升高，如高敏C反应蛋白（hsCRP）和IL-6，并且有很高的风险发生威胁生命的动脉粥样硬化事件以及肾功能丧失，因此可能会从IL-6抑制中受益。

observations

The Ziltivekimab Cardiovascular Outcomes Trial (ZEUS; NCT05021835) will determine the safety and efficacy of IL-6 inhibition with ziltivekimab among patients with atherosclerotic cardiovascular disease (ASCVD), CKD, and systemic inflammation.

Ziltivekimab心血管结果试验（ZEUS; NCT05021835）将确定在动脉粥样硬化性心血管疾病（ASCVD）、慢性肾脏病（CKD）和系统性炎症患者中使用ziltivekimab抑制IL-6的安全性和有效性。

ZEUS is a multinational, double-blind, placebo-controlled, event-driven, randomized clinical trial inclusive of 6376 participants with ASCVD, CKD, and an hsCRP level greater than or equal to 2 mg/L who were randomized in a 1:1 fashion to receive either ziltivekimab, 15 mg, administered subcutaneously every month or matching placebo.

ZEUS是一项多国参与的、双盲的、安慰剂对照的、事件驱动的、随机临床试验，纳入了6376名ASCVD、CKD患者和hsCRP水平大于或等于2 mg/L的参与者，这些参与者以1:1的方式随机分配，每月皮下注射15 mg的ziltivekimab或匹配的安慰剂。

At randomization, mean age was 69.5 years, 27.5% were female, 92.0% had hypertension, 65.7% had diabetes, and 41.3% had heart failure.

随机分组时，平均年龄为69.5岁，27.5%为女性，92.0%患有高血压，65.7%患有糖尿病，41.3%患有心力衰竭。

At baseline, the mean estimated glomerular filtration rate (eGFR) was 44.5 mL/min/1.73 m2, mean low-density lipoprotein cholesterol level was 77.7 mg/dL, median hsCRP level was 4.5 mg/L, and median IL-6 level was 4.9 pg/mL.

基线时，平均估算肾小球滤过率（eGFR）为44.5 mL/min/1.73 m2，平均低密度脂蛋白胆固醇水平为77.7 mg/dL，中位数高敏C反应蛋白（hsCRP）水平为4.5 mg/L，中位数白细胞介素-6（IL-6）水平为4.9 pg/mL。

At enrollment, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were being used by 36.8% and 11.3% of the cohort, respectively.

入组时，钠-葡萄糖共转运蛋白-2抑制剂和胰高血糖素样肽-1受体激动剂分别被36.8%和11.3%的队列使用。

The primary outcome is 3-point major adverse cardiovascular events.

主要结果是3点主要不良心血管事件。

Secondary cardiovascular outcomes include (1) an expanded major adverse cardiovascular event outcome including hospitalization for unstable angina requiring urgent coronary revascularization, (2) hospitalizations for heart failure or urgent heart failure visits or cardiovascular death, and (3) all-cause mortality.

次要心血管结果包括 (1) 扩展的主要不良心血管事件结果，包括需要紧急冠状动脉血运重建的不稳定型心绞痛住院，(2) 心力衰竭住院或紧急心力衰竭就诊或心血管死亡，以及 (3) 全因死亡率。

The secondary kidney outcome is a composite of greater than 40% decline in eGFR, eGFR less than 15 mL/min/1.73 m2, dialysis, kidney transplant, death from kidney disease, or cardiovascular death.

次要肾脏结果是大于40%的eGFR下降、eGFR小于15 mL/min/1.73 m2、透析、肾脏移植、肾脏疾病死亡或心血管死亡的复合结果。

conclusions_and_relevance

The ZEUS randomized clinical trial will formally test the hypothesis that IL-6 inhibition with ziltivekimab will lower incident cardiovascular event rates and potentially slow kidney decline among participants with known ASCVD, CKD, and elevated hsCRP.

ZEUS 随机临床试验将正式测试一个假设，即使用 ziltivekimab 抑制 IL-6 可以降低已知动脉粥样硬化性心血管疾病（ASCVD）、慢性肾脏病（CKD）和高敏 C 反应蛋白（hsCRP）升高的参与者的首次心血管事件发生率，并可能减缓肾脏衰退。

If successful, the ZEUS trial would provide a fully novel approach for prevention of myocardial infarction, stroke, cardiovascular death, and kidney function decline among high-risk patients with CKD.

如果 ZEUS 试验成功，它将为高风险慢性肾脏病（CKD）患者提供一种全新的预防心肌梗死、中风、心血管死亡和肾功能下降的方法。