Inflammatory Pathways in Coronary Artery Disease: Which Ones to Target for Secondary Prevention?

Coronary artery disease (CAD), the build-up of atherosclerotic plaques on the wall of blood vessels, causes adverse cardiovascular events. Secondary prevention focuses on treating patients with existing plaques to prevent disease progression. Recent studies have shown that inflammation is an independent risk factor that drives disease progression, and targeting inflammation could be an effective therapeutic strategy for secondary prevention. In this review, we highlighted the roles of several inflammatory pathways in rupture and erosion, two major processes through which established plaques lead to adverse cardiovascular events. In the past 15 years, numerous clinical trials have tested the therapeutic potential of targeting these pathways, including neutralizing inflammatory cytokines and blocking signaling transduction of the inflammatory pathways. Only colchicine was approved for clinical use in patients with CAD. This is primarily due to the multifaceted roles of inflammatory pathways in disease progression. Commonly used pre-clinical models provided robust information for the onset of early disease but limited understanding of the inflammatory network in established plaques. This review will summarize lessons learned from successful and failed clinical trials to advocate for assessing inflammation in established plaques before designing therapeutics for secondary prevention.