Inflammation Drug Fails to Cut Heart Attack Risk
Adults with heart disease and inflammation saw no drop in heart events in a large global trial of ziltivekimab.
Updated on Nov. 9, 2026 in Heart Disease
A global phase 3 trial called ZEUS found that ziltivekimab, a drug targeting the inflammatory protein interleukin-6 (IL-6), lowered IL-6 levels but did not reduce heart attacks, strokes, or cardiovascular deaths compared with placebo. The results matter most for adults with established heart disease and systemic inflammation who had hoped anti-inflammatory drugs would offer a new way to lower cardiovascular risk.
Why it matters
Inflammation has been widely studied as a driver of heart disease alongside cholesterol and blood pressure, so a well-designed negative result shapes which anti-inflammatory approaches researchers pursue next. The ZEUS population was older, had significant kidney disease, and often had longstanding diabetes and heart failure, which may explain why results differed from earlier trials.
ZEUS is a global phase 3 randomized trial sponsored by Novo Nordisk and led by Paul Ridker of Mass General Brigham, testing ziltivekimab against placebo in people with atherosclerotic cardiovascular disease and systemic inflammation. The trial recorded 561 primary endpoint events in the treatment group versus 565 in the placebo group, with no statistically significant difference in outcomes.
The players
Paul Ridker
Cardiologist at Mass General Brigham who leads the ZEUS trial and has long studied inflammation as a driver of cardiovascular disease.
Novo Nordisk
Danish pharmaceutical company that sponsored the ZEUS trial and develops therapies for diabetes, obesity, and cardiovascular conditions.
American Heart Association
Leading U.S. nonprofit that funds cardiovascular research and hosts its annual Scientific Session, where the ZEUS results were presented.
The details
Ziltivekimab works by blocking interleukin-6, a signaling protein that promotes inflammation in the body, and the drug successfully lowered IL-6 levels in participants. Lower inflammation did not, however, translate into fewer heart attacks, strokes, or cardiovascular deaths over the course of the trial. Safety results showed no adverse effect on total mortality, though a small increase in infection rates was observed. Researchers have suggested possible explanations, including differences between the ZEUS population and previous trial populations and the distinction between IL-6 and other inflammatory targets.
Timeline
November 8, 2026: ZEUS findings were presented at the American Heart Association Scientific Session and published in the New England Journal of Medicine.
Health Landscape
Anti-inflammatory therapy for heart disease has moved from a theoretical idea after the CANTOS trial to a testing ground for multiple drugs, and ZEUS is one of the largest tests of an IL-6 approach. The negative result places IL-6 inhibition alongside other ongoing trials that focus on modifiable, earlier-stage disease rather than advanced established illness.
If you have established heart disease, these results mean that lowering inflammatory markers alone is not yet a proven way to prevent heart attacks or strokes, so it is worth keeping proven risk-reduction steps in focus. Anyone with heart disease or kidney disease who is weighing new treatment options should discuss how these findings apply to their own case with their doctor.
The takeaway
Reducing inflammation did not translate into fewer heart attacks or strokes in the ZEUS trial, showing that the link between inflammation and heart events is more complicated than early hopes suggested. Readers managing heart disease should keep proven prevention strategies central and ask their physician about which emerging treatments may be relevant to them.
Further reading
For broader background on how inflammation and other factors shape cardiovascular risk, explore our Heart Disease coverage.
More information
Read the full NEJM ZEUS trial publication on ziltivekimab for the complete study design and results.
