Persistent inflammatory residual risk despite aggressive cholesterol-lowering therapy: what is next?

To briefly summarize recently published evidence on the possible therapeutic modulation of inflammatory processes in atherosclerotic cardiovascular disease (ASCVD), focusing on the rationale for an additional randomized clinical trial, targeting both persistently elevated cholesterol and inflammatory residual risk and critically discuss still open issues and future perspectives with regard to treatment allocation.Several large-scale clinical trials over the past few years have advanced our understanding of the role of inflammation in atherosclerosis, demonstrating that targeting the NLRP3 inflammasome and the IL-1β pathway indeed represent a new avenue to reduce residual risk in patients with ASCVD. However, despite optimal lipid-lowering therapy and novel options to modulate residual inflammatory risk, there are still a large number of individuals, being at high risk for recurrent ASCVD events.The integration of a dual target strategy aimed at lowering the inflammatory burden in combination with aggressive lipid-modifying for those at high/very high ASCVD risk may hold potential to significantly improve patient care. However, a number of questions related to the design of such 2 × 2 factorial trial still needs to be answered.