Heart researchers unpack neutral findings from ZEUS, an anti-inflammatory clinical trial

Key Points:

• The ZEUS phase 3 trial tested ziltivekimab, an IL-6 inhibitor, in patients with atherosclerotic cardiovascular disease but found no reduction in cardiovascular events despite lowering IL-6 levels, suggesting IL-6 targeting may be more complex than anticipated.
• Differences in patient populations, such as older age and more advanced disease with kidney issues and diabetes in ZEUS compared to prior trials like CANTOS, may have influenced the neutral results, indicating advanced disease might limit the benefits of IL-6 inhibition.
• Previous research (CANTOS) showed that targeting upstream inflammation via IL-1b reduced heart attacks and strokes, prompting suggestions to explore upstream targets like the NLRP3 inflammasome rather than downstream IL-6 inhibition.
• Although ziltivekimab did not improve outcomes, low-dose colchicine, an established anti-inflammatory drug, has proven benefits in reducing cardiovascular risk but remains underused in patients with stable atherosclerosis.
• Researchers emphasize the importance of continued trials to identify effective anti-inflammatory therapies and highlight the role of lifestyle changes and existing medications with anti-inflammatory effects, such as statins and GLP-1 receptor agonists, in cardiovascular prevention.