Anti-Inflammatory Drug Lowered Inflammation but Not Heart Attacks in a Large Trial

Mass General Brigham, which led the phase 3 ZEUS trial, says the drug ziltivekimab lowered the inflammatory signal it was built to block but left rates of heart attack, stroke and cardiovascular death unchanged. The trial's main measure, a combined count of those three events, occurred in 561 participants given the drug and 565 given a placebo, a difference that was not statistically significant.

ZEUS tested whether blocking interleukin-6 (IL-6), a molecule that drives inflammation, would prevent heart attacks and strokes in people who already have narrowed arteries and body-wide inflammation. An earlier trial led by the same researcher, Paul Ridker of Mass General Brigham, lowered rates of repeat heart attacks and strokes by blocking a different signal, IL-1b. "The critical question is which drug works best in which patients," Ridker said.

The release says Novo Nordisk sponsored ZEUS, and that the results were presented at the American Heart Association Scientific Session and published Nov. 7, 2026, in the New England Journal of Medicine. The people enrolled were a decade older than those in the earlier trial, had significant kidney disease, and often had long-standing diabetes and heart failure. The drug brought no increase in deaths from any cause and a small rise in infections.

"Given our neutral findings, one logical next step is to move upstream, instead of downstream, to find the right target," Ridker said, pointing to drugs in development that act earlier in the pathway. He added that "it remains quite possible that downstream IL-6 inhibition is in fact effective, but that ZEUS targeted the wrong patient population." The release says the authors conclude that further trials are needed to work out how, and in whom, anti-inflammatory treatment lowers risk.

The release also points to colchicine, a generic anti-inflammatory drug the US Food and Drug Administration has approved to lower rates of heart attack and stroke. The LoDoCo2 and COLCOT trials have already shown that it reduces cardiovascular risk in patients with stable narrowed arteries, and Ridker said such drugs are underused today.