An Update on Inflammation in Atherosclerosis: How to Effectively Treat Residual Risk

Purpose: This study reviewed the contribution of inflammation to atherosclerotic cardiovascular disease (ASCVD), which has gained widespread recognition in recent years. Methods: This critical review evaluated how recent publications and ongoing clinical trials in atherosclerotic inflammation will affect clinical care. Findings: Key trials, including CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) with canakinumab (interleukin-1β inhibition), and COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low Dose Colchicine 2) with colchicine, have shown that suppressing inflammation can improve outcomes in ASCVD. Cholesterol crystals play an important role in activating the NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome and subsequent cytokine cascade. Inflammation contributes to significant residual risk after optimal lipid-lowering therapy. High-sensitivity C-reactive protein is a recognized biomarker of residual risk, and newer biomarkers such as the neutrophil to lymphocyte ratio may add additional information. The role of lipoprotein(a) as a proinflammatory agent or possible inflammatory biomarker is under investigation. The contribution of clonal hematopoiesis of indeterminate potential and trained immunity are in the early stages of investigation. Ongoing clinical trials of suppressing inflammation with NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome inhibition (colchicine) and alternative approaches with downstream interleukin-6 ligand inhibition (ziltivekimab) will expand the evidence base for the use of anti-inflammatory agents in ASCVD. Implications: Based on current evidence and ongoing clinical trials, targeting inflammation alongside optimal lipid lowering is likely to be central to the future treatment of ASCVD. (Clin Ther.