ZEUS: ziltivekimab lowered inflammation but not heart attacks or strokes

The phase 3 ZEUS trial (Ziltivekimab Cardiovascular Outcomes Study), led by Paul M. Ridker of Mass General Brigham and Harvard Medical School, was presented on 7 November 2026 at the American Heart Association Scientific Sessions and published the same day in the New England Journal of Medicine. It tested monthly subcutaneous ziltivekimab 15 mg, a monoclonal antibody that blocks interleukin-6 (IL-6), against placebo in adults with atherosclerotic cardiovascular disease, clinically significant chronic kidney disease and elevated inflammation (high-sensitivity C-reactive protein, or hs-CRP, of at least 2 mg/L).

Main findings

Researchers enrolled 6,376 adults at 757 sites in 38 countries between September 2021 and December 2024 (average age 69.4 years; 27.5% women). Besides ASCVD and CKD, 92% had high blood pressure, nearly 66% had type 2 diabetes and 42% had heart failure; 92.6% were already on cholesterol-lowering drugs. Treatment lasted a median of 29.1 months.

Compared with placebo, ziltivekimab lowered hs-CRP by 64% and IL-6 by 76%. The primary endpoint of heart attack, stroke or cardiovascular death occurred in 561 participants on ziltivekimab and 565 on placebo. Healio, citing the presentation, reported rates of 17.6% versus 17.7% over a median 33 months of follow-up (hazard ratio 0.99, 95% CI 0.88–1.11; P = .84). All-cause deaths were 538 versus 542 (Healio: 16.9% versus 17%). Serious infections were more common with ziltivekimab (20% versus 18% in the AHA release; Healio reported 20.4% versus 17.9%). Overall serious adverse event rates were similar (54% in both groups, per Healio).

Ridker said ZEUS participants were older and sicker than those in the earlier CANTOS trial of IL-1β inhibition, with more advanced kidney disease, longstanding diabetes and heart failure, and that the disease may have been too advanced to modify.

Limits — not personal medical advice

Participants already had advanced ASCVD and CKD, so the results may not apply to earlier-stage disease. The trial was funded by Novo Nordisk, which makes ziltivekimab. A small increase in serious infections is a known concern with anti-inflammatory therapy. Neutral results for this drug in this population do not mean all anti-inflammatory approaches are ineffective; the authors pointed to prior evidence from other agents and called for further trials. This is not personal medical advice — talk to your doctor about heart and kidney care.