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Like cholesterol, inflammation causally contributes to the risk of cardiovascular disease, but findings from the clinical trial ZEUS indicate that the road to targeting inflammation may be less straightforward than once thought. ZEUS, a global phase 3 clinical trial led by Mass General Brigham researcher Paul Ridker, M.D., tested a drug that targets interleukin-6 (IL-6), a downstream inflammatory molecule. IL-6 inhibitors are commonly used to treat autoimmune disorders. However, while the new drug known as ziltivekimab lowered IL-6 levels, it did not reduce cardiovascular event rates compared to placebo.

In a late-breaking clinical trial presentation at the American Heart Association Scientific Session and in a simultaneous publication in New England Journal of Medicine, Ridker and colleagues detail the findings and lay out several potential explanations, including differences between the population enrolled in ZEUS and those enrolled in previous trials and the difference between IL-6 and other inflammation targets.

"The findings from ZEUS illustrate why clinical trials are so important: We don't yet have all of the answers and science is often about trial and error," said Ridker. "We already know from prior studies that targeting inflammation can reduce rates of heart attack and stroke. The critical question is which drug works best in which patients."

Previous work in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study ( CANTOS ), also led by Ridker, showed that targeting a midstream interleukin known as IL-1b significantly lowered rates of recurrent heart attacks and strokes.

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