Review of Recent Literature and Updates in Nonstatin Cholesterol Management

The guidelines for cholesterol management have been updated over the years from treat-to-target using any drug class to emphasis on statins without treatment targets to a hybrid of the 2 approaches. The most recent guideline updates include newer nonstatin lipid-lowering therapies (LLTs), low-density lipoprotein cholesterol (LDL-C) reduction goals, and LDL-C thresholds considering secondary prevention and cardiovascular risk. Although statins have been the mainstay of LLT for years, newer pharmacological agents such as proprotein convertase subtilisin-kexin type 9 inhibitor(s) (PCSK9i) monoclonal antibodies, small interfering RNA PCSK9i, and bempedoic acid to optimize LDL-C levels may be underutilized in clinical practice. To provide an updated review for clinicians, we performed a literature search in PubMed for articles published from January 1, 2000, to August 31, 2023, that included the terms cholesterol, LLT, bempedoic acid, inclisiran, or PCSK9 inhibitor. Studies were selected for inclusion according to relatedness to cholesterol management and outcomes with novel LLT agents. Optimization of statins can improve the lipid profile and contribute to primary and secondary atherosclerotic cardiovascular disease (ASCVD) prevention. The newest guidance combines anticipated LDL-C reduction from statins and LDL-C thresholds for primary and secondary prevention. Nonstatin agents such as PCSK9i monoclonal antibodies, small interfering RNA PCSK9i, and bempedoic acid are safe and effective LLTs that can be used in addition to statin therapy for additional LDL-C lowering and prevention of ASCVD. Additionally, these nonstatin agents are reasonable to initiate in patients who have not been able to tolerate statins due to myalgias, rhabdomyolysis, or contraindications. Cost may be a barrier to initiating these agents for patients who are underinsured or uninsured. Clinicians should reference the most up-to-date guidance for LLT for primary and secondary prevention of ASCVD. Additionally, clinicians must diligently continue to optimize statin and nonstatin LLT to improve cardiovascular health outcomes.