Challenges in achieving LDL cholesterol targets and novel approaches to lipid lowering.

Low-density lipoprotein cholesterol (LDL-C) is the pre-eminent target for the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). Despite the expansive evidence supporting therapeutic reductions in LDL-C with statin therapy, many high-risk patients do not achieve guideline-recommended treatment targets resulting in avoidable cardiovascular events and higher healthcare expenditures. Underutilization of effective LDL-C lowering is exacerbated by low adherence to statin therapy even among patients following an acute coronary event. Adjunctive therapies such as ezetimibe and PCSK9 monoclonal antibodies remain underutilized, and polypharmacy regimens used for the treatment of cardiovascular disease further increase challenges for patients. Although cardiovascular outcomes data are lacking, inclisiran, a small-interfering RNA (siRNA) targeting PCSK9 mRNA, is available for clinical use. Novel implementation approaches offer the opportunity for more durable or even potentially permanent solutions for lipoprotein-associated cardiovascular disease risk. As an adjunct to statins, these novel approaches may offer more durable approaches for the prevention of ASCVD events. In this review, we discuss the challenges of current LDL-C lowering therapies, achieving LDL-C targets and the necessity of novel approaches.