Reversal of Atherosclerotic Plaque Growth and Vulnerability: Effects of Lipid-Modifying and Anti-Inflammatory Therapeutic Agents

Abstract

Atherosclerotic plaque development constitutes the primary substrate of coronary artery disease (CAD) and is the outcome of an intricate process involving endothelial damage, inflammation, and lipid retention. The clinical efficacy of many lipid-lowering therapies in patients with CAD has been well established. Over the past few decades, a substantial and significant advance regarding the use of invasive and non-invasive imaging modalities has been observed. Numerous studies have been conducted using these imaging techniques and have investigated the changes in morphology (e.g., atheroma volume) and composition (e.g., lipid burden, fibrous cap thickness, macrophage accumulation) at the plaque level that explain the improved clinical outcomes by various pharmacological interventions. Lipid-lowering agents, such as statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, demonstrate direct effects on plaque volume and composition that enhance plaque stabilization and/or regression beyond the reduction of low-density lipoproteins. An increasing amount of clinical research is also focused on the role of inflammation in plaque vulnerability and future adverse cardiac events. Consequently, there is a pressing need to explore therapeutic strategies that are capable of disrupting the inflammatory response as well as reducing atheroma burden and modifying high-risk plaque characteristics. This review provides a comprehensive analysis of the current evidence regarding the effects of traditional and novel therapeutic strategies targeting modification of the lipid profile and inflammatory processes on reversing plaque growth and attenuating vulnerable features, thereby promoting plaque stabilization and passivation.

Keywords: PCSK9; atherosclerosis; coronary artery disease; intravascular imaging; intravascular ultrasound; lipid-lowering therapies; optical coherence tomography; plaque regression; plaque stabilization; statins.

Figure 1

Lipid-lowering (focus on cholesterol) and anti-inflammatory therapeutic agents with their principal mechanism of action, and summary of their effects on atherosclerotic plaques leading to plaque regression and stabilization.