Nonstatin lipid-lowering agents
| Lipid-lowering agent | Mechanism of action | LDL-C reduction | When to consider using |
|---|---|---|---|
| Ezetimibe | Inhibits cholesterol absorption in the small intestine | 15%–22% (23%–25% in combination with a statin) | First-line agent if insufficient response seen with statins alone |
| PCSK9 inhibitor | Prevents PCSK9, an enzyme involved in the degradation of LDL receptors on liver cells, from binding to LDL receptors, reducing receptor degradation and, in turn, increasing LDL-C clearance | 55%–65%13 | Second-line agent if LDL-C targets are not met with statin and ezetimibe combination therapy Can be first line if > 25% reduction in LDL-C is required or patient is deemed very high riska |
| Inclisiran | Small interfering RNA that binds to messenger RNA of PCSK9, limiting production of the enzyme | 49.9%–52.3% | For patients deemed very high risk who are not achieving LDL-C targets on statins alone |
| Bempedoic acid | Decreases cholesterol synthesis in the liver by inhibiting adenosine triphosphate citrate lyase | 16.5% (36.2% in combination with ezetimibe) | For patients deemed very high risk who are not achieving LDL-C targets on statins alone |
| Evinacumab | Monoclonal antibody that inhibits angiopoietin-like 3, a protein that reduces the activity of lipases involved in lipid hydrolysis, thus increasing lipid metabolism | 47.1% | For patients with homozygous familial hypercholesterolemia |
| Lomitapide | Inhibits microsomal triglyceride transfer protein, which is involved in the assembly of apolipoprotein B and the production of very-low-density lipoprotein | 25%–51% | For patients with homozygous familial hypercholesterolemia |
↵aVery high risk: history of either multiple major atherosclerotic cardiovascular disease (ASCVD) events or 1 major ASCVD event with multiple high-risk factors (age > 65, heterozygous familial hypercholesterolemia, history of prior coronary artery bypass grafting or percutaneous coronary intervention outside of a major ASCVD event, diabetes, hypertension, chronic kidney disease, smoking, persistent LDL-C elevation despite therapy with maximum statin and ezetimibe, congestive heart failure history).2
LDL = low-density lipoprotein; LDL-C = low-density lipoprotein cholesterol; PCSK9 = proprotein convertase subtilisin/kexin type 9
Based on information from reference 3.