ZEUS Trial Results
Interleukin-6 inhibition showed no cardiovascular benefit in older patients with atherosclerotic cardiovascular disease and chronic kidney disease.
The findings emerged from the ZEUS trial presented at the American Heart Association Scientific Sessions 2026. Researchers evaluated the investigative monoclonal antibody ziltivekimab against placebo in a global study population.
Cardiovascular Inflammation Target
Paul M. Ridker said inflammation remains a viable therapeutic target despite the neutral trial outcome. He directed the Center for Cardiovascular Disease Prevention at Mass General Brigham in Boston.
“We already have proof that inflammation is targetable,” Ridker said. The 2017 CANTOS trial previously established inflammation as a modifiable cardiovascular risk factor.
Ziltivekimab Lowered Targeted Biomarkers Despite Missing Clinical Endpoints
The study enrolled 6,376 patients across more than 750 sites in 38 countries. Participants received monthly subcutaneous injections of 15 mg ziltivekimab or placebo over a median follow-up of 33 months.
Ziltivekimab successfully lowered targeted biomarkers despite missing clinical endpoints. Treatment yielded a 76% placebo-adjusted reduction in free circulating interleukin-6 and a 64% reduction in C-reactive protein at 24 months.
ZEUS results presented at #ScientificSessions26. Lowering interleukin-6 levels with ziltivekimab did not lower the risk of cardiovascular events in patients with ASCVD, CKD, and cardiovascular inflammation compared to placebo. pic.twitter.com/fPl0Dswe3G
Advanced Disease Challenges
Researchers examined why the ZEUS trial diverged from the positive results seen in the earlier CANTOS study. ZEUS enrolled a sicker patient population with a twofold higher mortality rate.
Chronic kidney disease served as a trial entry criterion, with 72% of participants exhibiting advanced disease. Ridker noted that the disease may have been too far advanced to respond to anti-inflammatory intervention.
Inflammation in the spotlight! ⁰#ESCTVOntheRoad 🚍 at #AHA26 @TokgozogluLale presents the primary results of ZEUS, the Ziltivekimab Cardiovascular Outcomes Trial. Watch the key takeaways🎬#ZEUS #Cardiology #Inflammation pic.twitter.com/dAJzbC9fZE
Future Research Direction
Priscilla Hsue, chief of the division of cardiology at the University of California at Los Angeles, emphasized the complexity of interleukin-6 receptor biology. She spoke as an invited discussant at the association meeting.
“The take-home message should not be that inflammation doesn’t matter,” Hsue said. Ongoing evaluations include the ARTEMIS study, which evaluates ziltivekimab for secondary prevention following a myocardial infarction with results expected in late 2027.
What Was the Primary Endpoint of the ZEUS Trial?
What was the primary endpoint of the ZEUS trial?
The trial tracked a three-point major adverse cardiovascular event endpoint that included cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.
How many patients experienced serious infections?
Serious infections occurred in 20.4% of patients in the ziltivekimab arm compared with 17.9% in the placebo group.
Which organization funded the study?
Novo Nordisk provided financial support for the ZEUS trial. The trial was published simultaneously in The New England Journal of Medicine.