Ziltivekimab did not reduce cardiovascular events in patients with atherosclerotic disease and kidney impairment
Primary endpointA 3-point major adverse cardiovascular event (MACE)
Where these numbers come from
“During a median follow-up of 33 months, a primary end-point event occurred in 561 patients (17.6%) in the ziltivekimab group and in 565 patients (17.7%) in the placebo group (hazard ratio, 0.99; 95% confidence interval, 0.88 to 1.11; P = 0.84).”
The publication
**In a randomized trial of patients with atherosclerotic cardiovascular disease, chronic kidney disease, and elevated inflammation, monthly ziltivekimab did not lower the risk of major adverse cardiovascular events compared with placebo. Over a median follow-up of 33 months, the primary endpoint occurred in 17.6% of those receiving ziltivekimab versus 17.7% on placebo (hazard ratio, 0.99; 95% confidence interval, 0.88 to 1.11).**
Who the findings apply to
The trial enrolled adults with established atherosclerotic cardiovascular disease, chronic kidney disease, and evidence of cardiovascular inflammation defined by a high-sensitivity C-reactive protein level of 2 mg per liter or higher.
Why this matters
The study tested whether neutralizing interleukin-6, an inflammatory cytokine, could reduce cardiovascular risk in a high-risk population already receiving standard care. The authors concluded that lowering interleukin-6 levels with ziltivekimab did not result in a lower risk of cardiovascular events than placebo.
What the study found
A total of 6376 patients were included in the full analysis population, with 3184 assigned to ziltivekimab and 3192 to placebo. The mean age was 69.4 years, and 27.5% were women.
Ziltivekimab significantly reduced inflammatory biomarkers at 24 months. The between-group difference in the median percent change was -76 percentage points for free interleukin-6 and -64 percentage points for high-sensitivity CRP compared with placebo.
The primary efficacy endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. During a median follow-up of 33 months, this event occurred in 561 patients (17.6%) in the ziltivekimab group and 565 patients (17.7%) in the placebo group.
The hazard ratio for the primary endpoint was 0.99 with a 95% confidence interval of 0.88 to 1.11, yielding a P value of 0.84, indicating no statistically significant difference between groups.
What the result does not establish
Serious adverse events occurred in 54.6% of patients receiving ziltivekimab and 54.8% of those on placebo. Serious infections were reported in 20.4% of the ziltivekimab group compared with 17.9% in the placebo group.
The study was funded by Novo Nordisk and registered as NCT05021835.
Authors’ conclusion
“Among patients with atherosclerotic cardiovascular disease, chronic kidney disease, and cardiovascular inflammation, a strategy of lowering interleukin-6 levels with ziltivekimab did not result in a lower risk of cardiovascular events than placebo.”
Trial registration
| Registered title | ZEUS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Cardiovascular Disease, Chronic Kidney Disease and Inflammation (ZEUS) |
|---|---|
| Registry status | Phase 3, interventional, active not recruiting |
| Lead sponsor | Novo Nordisk A/S |
| Registered size | 6,200 participants — planned enrolment (estimate). The abstract reports: 6376 patients |
| Where | 1,033 sites in 38 countries (Argentina, Australia, Belgium, Brazil, Bulgaria, Canada and 32 more) |
| Registered primary outcome |
|
- Start: Aug 2021
- Completion: Jun 2026 (estimated; this date has passed — check the registry)
- Primary completion: Jun 2026 (estimated; this date has passed — check the registry)
- Paper published: Nov 2026
ClinicalTrials.gov record as held by ENCLAI, last updated Nov 2025. The registry status may have changed since; the link shows the current record.
Study and sources
Interleukin-6 Inhibition with Ziltivekimab for Atherosclerotic Disease
Randomised trial · NEJM · 2026-11-07
Sources and limitations
- PubMed record PMID 43001751 (PubMed / NLM · 2026-11-11)
- Trial registry NCT05021835 (ClinicalTrials.gov · 2026-11-11)
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