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. 2026 Oct 5;17:1936459. doi: 10.3389/fphar.2026.1936459

FIGURE 1.

Infographic showing three types of LDL-C-lowering therapies: Cholesterol Absorption Inhibitors (hybutimibe, ezetimibe), PCSK9-Targeted Therapies (PCSK9 mAbs: evolocumab, alirocumab; siRNA: inclisiran), and Statins (atorvastatin, rosuvastatin, simvastatin, pravastatin, pitavastatin). Bempedoic acid ACL inhibitor is also noted. Cardiovascular outcome benefit is demonstrated for statins, ezetimibe, PCSK9 mAbs, and bempedoic acid, but not established for hybutimibe and inclisiran.

Mechanisms and Evidence Status of Contemporary LDL-C-Lowering Therapies. Statins inhibit hepatic cholesterol synthesis through HMG-CoA reductase, whereas bempedoic acid inhibits ATP-citrate lyase upstream of HMG-CoA reductase. Ezetimibe and hybutimibe reduce intestinal cholesterol absorption by targeting NPC1L1. PCSK9 monoclonal antibodies and inclisiran enhance LDL receptor availability through extracellular PCSK9 inhibition and hepatic PCSK9 synthesis inhibition, respectively. Cardiovascular outcome benefits have been demonstrated for statins, ezetimibe added to statin therapy, PCSK9 monoclonal antibodies, and bempedoic acid in selected populations. Hybutimibe currently has LDL-C-lowering efficacy data but no dedicated cardiovascular outcome trial, while cardiovascular outcome trials of inclisiran remain ongoing.