Interleukin-6: A Novel Risk Factor and Therapeutic Target in Coronary Artery Disease

Abstract Coronary artery disease (CAD) remains the leading cause of mortality worldwide despite advances in managing traditional risk factors such as hypertension and hyperlipidemia. Increasing evidence highlights the central role of inflammation in CAD pathogenesis, with interleukin-6 (IL-6) emerging as a key link between immune system activation and the development of atherosclerosis. Elevated IL-6 levels predict worse cardiovascular outcomes, independent of conventional risk factors. This review examines how IL-6 promotes endothelial dysfunction, plaque formation, and instability, and evaluates clinical evidence linking IL-6 to increased CAD risk. It also explores therapeutic strategies targeting the IL-6 pathway, focusing on randomized controlled trials of tocilizumab and ziltivekimab. Early results indicate that IL-6 inhibition can reduce systemic inflammation without major adverse effects, but these studies have been limited by small sample sizes and short follow-up periods. Ongoing phase 3 outcome trials, including ZEUS and HORIZON, will be critical for determining long-term safety and efficacy. Targeting IL-6 offers a promising new way to reduce inflammatory risk and improve long-term outcomes in CAD patients. Importantly, IL-6 inhibition has not yet been shown to reduce clinical cardiovascular events.