Unraveling the temporal sequence of coronary atherosclerosis modification with lipid-lowering therapies through intravascular imaging: a narrative review

The management of ischemic heart disease has evolved from a narrow focus on low-density lipoprotein cholesterol (LDL-C) reduction to a comprehensive strategy targeting the regression and stabilization of coronary atherosclerotic plaque. Intravascular imaging modalities, including intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near-infrared spectroscopy (NIRS), have been instrumental in characterizing the temporal sequence of plaque modification in response to lipid-lowering therapy. This review synthesizes evidence demonstrating that the effects on plaque are both time-dependent and agent-specific. Statins induce rapid plaque stabilization within weeks to months via mechanisms such asanti-inflammatory effects, fibrous cap thickening, and reduction of the lipid core. With prolonged treatment (months to years), statins promote plaque volume regression and facilitate a favorable shift in plaque composition towards a more stable, calcified phenotype. Non-statin agents further augment this regression. Ezetimibe, in combination with statins, provides synergistic LDL-C lowering and enhances plaque volume reduction. PCSK9 inhibitors, recognized as one of the most potent lipid-lowering agents currently available, have been shown in several studies to promote the regression of atherosclerotic plaques and reduce plaque volume. However, their effects on plaque composition-such as calcification, fibrous tissue, fibrofatty tissue, and necrotic core-remain controversial.