Effect of Omega-3 fatty acids, fibrates and PCSK9 inhibitors on atherosclerotic plaque burden, composition and stability: Insights from imaging.

Atherosclerotic plaque burden, composition, and stability are key determinants of acute cardiovascular events. Serial coronary imaging, including intravascular ultrasound (IVUS), optical coherence tomography (OCT), and coronary computed tomographic angiography (CCTA), enables mechanistic assessment of pharmacotherapeutic effects on plaque in vivo. This review synthesizes imaging evidence from three drug classes: omega-3 fatty acids, distinguishing eicosapentaenoic acid (EPA) monotherapy as icosapent ethyl (IPE) from EPA/DHA combinations; fibrates; and PCSK9 inhibitors. EPA monotherapy has been associated with plaque regression and features of stabilization across imaging modalities. IVUS trials show greater regression with EPA plus statin than statin alone, OCT studies demonstrate fibrous cap thickening, and the EVAPORATE trial reported reduced low-attenuation plaque with IPE compared with placebo. Exploratory analyses further suggest reductions in lipid-rich necrotic core and other vulnerability features. In contrast, EPA/DHA combination therapies have not demonstrated consistent plaque benefit, in line with neutral cardiovascular outcomes in STRENGTH and OMEMI. Fibrate imaging data remain limited, with evidence largely confined to historical angiographic studies. PCSK9 inhibitors produce robust plaque regression related to achieved LDL-cholesterol levels, with IVUS evidence from GLAGOV and OCT evidence from HUYGENS demonstrating both volumetric regression and fibrous cap stabilization. Overall, concordance between imaging findings and cardiovascular outcomes supports a role for coronary plaque imaging as a mechanistic bridge between pharmacological intervention and clinical risk reduction.