2024 KSoLA Update on New Lipid-Lowering Agents: Inclisiran and Bempedoic Acid

Abstract

Inclisiran and bempedoic acid (BA) are non-statin lipid-lowering agents that have been approved for use in the US and Europe. Inclisiran, a subcutaneously administered small interfering RNA targeting proprotein convertase subtilisin/kexin type 9 messenger RNA, is effectively delivered to the liver via lipid nanoparticles and conjugation. In several phase 3 trials, it has successfully reduced low-density lipoprotein cholesterol (LDL-C) by 50% and has an acceptable safety profile. Currently, the results of clinical outcome studies are awaited. While it is indicated for both primary and secondary cardiovascular prevention, it is selectively recommended after statin-based regimens. BA, an oral inhibitor of adenosine triphosphate-citrate lyase, decreases cholesterol production and enhances LDL uptake by hepatocytes. This enzyme is absent in muscle cells, and BA has fewer muscle-related adverse events. In clinical trials, it lowered LDL-C by 17%-21% compared to placebo and showed a clinical outcome benefit in patients with statin intolerance. This agent modestly increases the incidence of gout and cholelithiasis. For primary and secondary prevention, it may be recommended as a non-first-line agent, either alone or in combination therapy.