Novel approaches to lipid lowering

The focus of this review are the novel and future approaches to reduce the cardiovascular (CV) residual risk by reducing the apoB-containing lipoproteins levels. We assume that in the clinical practice a combination therapy based on the use of high intensity statins, ezetimibe, bempedoic acid, mAbs anti PCSK9 or Inclisiran may reduce most of the cardiovascular risk associated with the apoB containing lipoproteins and may contribute to achieve the LDL-Cholesterol (LDL-C) goal in the majority of individuals at high and very high risk. However we can assume that a proportion of well treated patients will develop new cardiovascular events. Many factors such as the genetic background, the pre-existing burden of disease and the residual risk attributable to triglycerides, inflammation, coagulation and platelets may explain this recurrence of events. We discuss some novel options to reduce the residual risk due to the two main apoB-containing lipoproteins, LDL-C and Lp(a), that are: -the newest-generation CETP inhibitor, Obicetrapib; the oral PCSK9 inhibition; the novel approaches to reduce Lp(a) plasma levels (antisense oligonucleotides-ASO; rna interfering-Sirna; assembly inhibition-; the PCSK9 gene editing.