Inflammation and atherosclerotic cardiovascular disease: where do we go from here?

Low-grade systemic inflammation, as determined by high-sensitivity C-Reactive Protein (hsCRP), plays a significant role in the progression and development of atherosclerotic cardiovascular disease (ASCVD) and is recognized as a risk enhancer for increased incidence of major adverse cardiovascular events (MACE). (In 2024, the US Food and Drug Administration approved colchicine, as the first anti-inflammatory agent for secondary cardiovascular prevention. While this step signified a translational milestone, recent neutral colchicine trials such as CLEAR- SYNERGY, have reignited controversy regarding the overall efficacy of colchicine, and the need for alternative anti-inflammatory therapies. As the understanding of inflammation's role in atherosclerosis grows, questions persist about the best management strategies and future therapeutic options. This review aims to provide an updated summary that includes insights from recent key trials, explores investigational anti-inflammatory treatments, and discusses considerations for future trial designs.

This review will encompass recent trials involving colchicine, IL-1 antagonists, and interluekin-6 Inhibitors.

In this review, we will discuss mechanisms of inflammation as they pertain to ASCVD, significant contemporary trials, novel anti-inflammatory therapies, and considerations for future trial designs.