Inflammation and Immune Mediators in the Context of Atherosclerotic Cardiovascular Disease and Percutaneous Coronary Intervention: Implications for Therapeutics

Atherosclerotic cardiovascular disease (CVD) remains a leading cause of worldwide morbidity and mortality, despite well-established/effective pharmacological therapies. A substantial component of the residual risk is inflammatory. The importance of inflammation and immune mediators in the pathophysiology has been recognised over the past two decades and, importantly, treatment with percutaneous coronary intervention (PCI) also results in an inflammatory response and associated adverse outcomes. Multiple biochemical pathways have been implicated with various identified biomarkers, such as high-sensitivity C-reactive protein which is now recognised as a marker of cardiovascular risk. Proteins such as interleukins (IL) IL-1 and IL-6 or larger protein complexes such as the NLRP3 inflammasome all play a key role in both the pathophysiology of atherosclerosis and inflammation relating to PCI. This knowledge has led to advances in pharmacological therapies and multiple pre-clinical and clinical trials, but to date, colchicine is the only treatment with sufficiently robust evidence from large-scale clinical trials to be recommended in multinational guidelines. Other therapies at present lack this level of evidence, and identification of other potential therapies is an important next step in treating inflammation post-PCI. Furthermore, the potential routine use of colchicine periprocedurally for PCI and its biochemical and clinical effects in this context are not yet fully established, requiring further investigation to identify its effect on specific inflammatory mediators and whether this translates to clinical outcomes.