Anti-inflammatory therapy targeting interleukin-6 (IL-1β) with ziltivekimab (a monoclonal antibody) did not lower risks of cardiovascular events compared with placebo in high-risk patients with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) and systemic inflammation, based on findings from the ZEUS trial presented at AHA 2026 and simultaneously published in NEJM.

The multinational, double-blind trial randomly assigned 6,376 patients to receive either subcutaneous ziltivekimab (15 mg once monthly) or placebo. The mean age of participants was 69 years and roughly 28% were women.

Over a median follow-up period of 33 months, results indicated no significant difference in the primary endpoint of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke across the ziltivekimab and placebo groups (17.6% vs. 17.7%, respectively). The between-group difference in the median percent change in the levels of inflammatory biomarkers at 24 months among patients receiving ziltivekimab compared with those receiving placebo was −76 percentage points for free IL-1β and −64 percentage points for high-sensitivity CRP, researchers said.

“In ZEUS, we found that treatment with ziltivekimab … resulted in a greater decrease in IL-1β and high sensitivity CRP levels than placebo; however, there was no evidence of a reduction in cardiovascular events with ziltivekimab as compared with placebo among [this] high-risk population of patients,” said Paul M. Ridker, MD, MPH, FACC, et al.

In presenting the findings, Ridker and colleagues also noted the contrast with results from the CANTOS trial, in which IL-1β inhibition with canakinumab 150 mg every 3 months significantly reduced recurrent cardiovascular events vs. placebo.

Although both trials enrolled patients with established ASCVD and elevated high-sensitivity CRP, they said ZEUS studied a substantially higher-risk population with clinically important CKD, a high burden of comorbidities like diabetes and heart failure, and an average age approximately 10 years older than the CANTOS population.

Clinical Topics: Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: AHA Annual Scientific Sessions, AHA26, Interleukin-6, Renal Insufficiency, Chronic, Myocardial Infarction, Heart Failure, Biomarkers, Diabetes Mellitus, Stroke, Interleukin-1