Challenges in the Choice of Nonstatin Medications for Low‐Density Lipoprotein‐C Lowering for Cardiovascular Risk Reduction

Atherosclerotic cardiovascular diseases continue to be a leading cause of death globally. Although statin medications remain the cornerstone of treatment for lowering low‐density lipoprotein cholesterol and reducing cardiovascular risk, there is a proportion of patients in whom treatment with statins may not achieve the guideline recommended low‐density lipoprotein cholesterol targets despite using maximally tolerated doses, or for various reasons, patients are unable or unwilling to intensify or continue statins. In these instances, use of nonstatin medications like ezetimibe, bempedoic acid, or PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors (alirocumab, evolocumab, inclisiran) in addition to maximally tolerated statin therapy can lead to additional lowering of low‐density lipoprotein cholesterol and beneficial reductions in cardiovascular events. This review provides an overview of the evidence supporting the use of nonstatin low‐density lipoprotein cholesterol lowering medications for cardiovascular risk reduction and practical considerations for the use of these agents.