Emerging New Lipid-Lowering Therapies in the Statin Era

Abstract

Statins have become the backbone of lipid-lowering therapy today by dramatically improving cardiovascular (CV) outcomes. Despite well-controlled low-density lipoprotein cholesterol (LDL-C) through statins, up to 40% patients still experience CV diseases. New therapeutic agents to target such residual cholesterol risk by lowering not only LDL-C but triglyceride (TG), TG-rich lipoproteins (TRL), or lipoprotein(a) (Lp[a]) are being newly introduced. Proprotein convertase subtilisin/kexin type 9 (PCSK9) small interference RNA (siRNA) and bempedoic acid therapies adding to statin therapies have shown additional improvement in CV outcomes. Recent trials investigating eicosapentaenoic acid to patients with high TG despite statin therapy have also demonstrated significant CV benefit. Antisense oligonucleotide (ASO) therapies with hepatocyte-specific targeting modifications are now being newly introduced with promising lipid-lowering effects. ASOs targeting TG/TRL, such as angiopoietin-like 3 or 4 (ANGPTL3 or ANGPTL4), apolipoprotein C-III (APOC3), or Lp(a) have effectively lowered the corresponding lipids without requiring high or frequent doses. Clinical outcomes from such novel therapeutics are yet to be proven. In this article, we review emerging therapeutics targeting LDL-C, TG, TRL, and Lp(a) to reduce the residual risk.