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Targeting inflammation didn't translate to fewer heart attacks. The ZEUS trial found that ziltivekimab — a novel IL-6 inhibitor — dramatically reduced inflammatory markers in high-risk patients with atherosclerosis and chronic kidney disease, but failed to lower major adverse cardiovascular events compared to placebo. Researchers say the findings raise important questions about which patients and which inflammatory targets may actually move the needle.
The ZEUS trial had a compelling hypothesis: block interleukin-6 (IL-6), a key inflammatory molecule, and reduce cardiovascular (CV) events in high-risk patients. The results, presented at the American Heart Association Scientific Sessions and published in The New England Journal of Medicine, told a more complicated story.
Ziltivekimab (Novo Nordisk), a once-monthly injectable IL-6 inhibitor, was tested in 6,376 adults with established atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease, and elevated inflammation markers. While the drug dramatically reduced inflammation, it did not lower the rate of major adverse CV events (MACE) — including CV death, nonfatal heart attack, or nonfatal stroke.
By the Numbers:
Why it matters: The trial doesn't close the door on inflammation as a CV target — it redirects the conversation. Experts now point to upstream targets like the NLRP3 inflammasome and suggest testing IL-6 inhibitors in lower-risk populations, where the disease may still be modifiable.
