CHICAGO, Nov. 7, 2026 – A phase III clinical trial called ZEUS has found that ziltivekimab, a monoclonal antibody that blocks the inflammatory signaling protein interleukin-6, did not significantly reduce the combined risk of heart attack, stroke or cardiovascular death in very high-risk adults with atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease. The results were presented at the American Heart Association’s Scientific Sessions 2026 and simultaneously published in The New England Journal of Medicine.
The trial, which included more than 6,300 adults across 38 countries, tested whether reducing inflammation with ziltivekimab could lower cardiovascular risk in a population with limited treatment options. Participants had confirmed ASCVD, clinically significant chronic kidney disease, and elevated high-sensitivity C-reactive protein (hs-CRP) levels. Many also had Type 2 diabetes, hypertension and heart failure.
Despite lowering hs-CRP by 64% and interleukin-6 by 76% compared to placebo, the primary endpoint of heart attack, stroke or cardiovascular death occurred in 561 participants on ziltivekimab and 565 on placebo. Overall deaths were 538 in the ziltivekimab group and 542 in the placebo group. Serious infections were more common with ziltivekimab (20% vs. 18%), a known risk of anti-inflammatory medications.
“While the lack of clinical benefit in ZEUS is disappointing, we already know from prior research that targeting inflammation can significantly reduce cardiovascular risk, so it’s important not to overinterpret these findings,” said lead study author Paul M. Ridker, M.D., M.P.H., FAHA, director of the Center for Cardiovascular Disease Prevention at Mass General Brigham. He noted that participants had advanced disease that may have been “too little, too late” for the treatment to show benefit.
The findings underscore the need for continued research into anti-inflammatory therapies. Ridker said ongoing and planned trials will explore downstream interleukin-6 inhibition in patients with earlier-stage disease and upstream targeting of the NLRP3 inflammasome. “It is a very exciting time for inflammation biology and heart disease,” he said.
For patients and clinicians, the results reinforce the importance of measuring inflammation and managing overall cardiovascular risk. The American Heart Association’s 2026 guideline for cardiovascular-kidney-metabolic (CKM) syndrome highlights the connections between heart disease, kidney disease, diabetes and obesity, and the need to manage these conditions together. The Association’s Life’s Essential 8 outlines steps such as eating a healthy diet, staying active, avoiding tobacco and managing blood pressure, cholesterol and blood sugar.
The ZEUS trial was funded by Novo Nordisk. Full disclosures are listed in the manuscript. The American Heart Association receives more than 85% of its revenue from sources other than corporations, and its financial information is available here.
