Ezetimibe functions by inhibiting cholesterol absorption in the small intestine. It achieves this by selectively binding to the transmembrane protein Niemann–Pick C1-like 1 (NPC1L1) on the brush border of enterocytes. By binding to NPC1L1, ezetimibe prevents the uptake of cholesterol-rich micelles from the intestinal lumen into enterocytes, thereby reducing the amount of cholesterol absorbed from the diet into the bloodstream.

Bempedoic acid acts by inhibiting adenosine triphosphate-citrate lyase (ACL), an enzyme involved in cholesterol biosynthesis. By targeting ACL, bempedoic acid disrupts the production of mevalonate, a precursor molecule in cholesterol biosynthesis. This inhibition occurs upstream of HMG-CoA reductase, providing an alternative mechanism for reducing cholesterol synthesis in addition to statins.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as alirocumab, evolocumab, and bococizumab function by blocking the activity of PCSK9, a serine protease involved in LDL receptor degradation. By inhibiting PCSK9, these monoclonal antibodies prevent the degradation of LDL receptors on hepatocytes, thereby increasing the availability of LDL receptors for binding and uptake of LDL particles from the bloodstream, ultimately resulting in decreased LDL cholesterol levels.

Inclisiran is a small interfering RNA (siRNA) that targets PCSK9 messenger RNA (mRNA). By binding to PCSK9 mRNA with the assistance of the RNA-induced silencing complex (RISC), inclisiran inhibits the translation of PCSK9 mRNA into PCSK9 protein. This results in reduced levels of PCSK9 protein, leading to increased expression of LDL receptors on hepatocytes and enhanced clearance of LDL cholesterol from the bloodstream.

Mipomersen is an antisense oligonucleotide (ASO) that targets the mRNA encoding apolipoprotein B-100 (apo-B 100). By binding to apo-B 100 mRNA, mipomersen inhibits its translation into apo-B 100 protein, which is a major component of LDL particles. As a result, mipomersen reduces the production of LDL particles in the liver, leading to decreased levels of circulating LDL cholesterol.

Cholesteryl ester transfer protein (CETP) inhibitors, including dalcetrapib, evacetrapib, anacetrapib, and torcetrapib, function by inhibiting the activity of CETP. CETP mediates the transfer of cholesteryl esters from high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL), as well as the transfer of triglycerides from LDL and VLDL to HDL. By inhibiting CETP, these medications increase HDL cholesterol levels and decrease LDL cholesterol levels, ultimately leading to improved lipid profiles.

Pelacarsen is an antisense oligonucleotide (ASO) that specifically targets the mRNA of the LPA gene, which encodes lipoprotein(a) [Lp(a)]. By binding to LPA mRNA, pelacarsen inhibits its translation into Lp(a) protein. Elevated levels of Lp(a) are associated with an increased risk of cardiovascular disease, making pelacarsen a potential therapeutic option for lowering Lp(a) levels and reducing cardiovascular risk.

Olpasiran, SLN360, lepodisiran, and muvalaplin are small interfering RNAs (siRNAs) that target the mRNA encoding apolipoprotein A (apo-A). These siRNAs, when incorporated into the RNA-induced silencing complex (RISC), bind to apo-A mRNA and inhibit its translation into apo-A protein. Apo-A is a major component of high-density lipoprotein (HDL) particles. By reducing the production of apo-A, these siRNAs have the potential to modulate HDL metabolism and improve lipid profiles.

Omega-3 fatty acids, such as eicosapentaenoic acid (EPA), when incorporated into cell membranes, competes with arachidonic acid for the production of eicosanoids, leading to the synthesis of less inflammatory and thrombogenic mediators. Additionally, EPA activates peroxisome proliferator-activated receptors (PPARs), which regulate gene expression involved in lipid metabolism, inflammation, and vascular function. By modulating these pathways, omega-3 fatty acids exert anti-inflammatory, anti-thrombotic, and anti-arrhythmic effects, ultimately contributing to improved cardiovascular outcomes.

Fibrates exert their pharmacological effects primarily through activation of the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARα). Upon activation, PPARα modulates the transcription of genes involved in lipid metabolism, including those encoding apolipoprotein A-I (apoA-I), apolipoprotein A-II (apoA-II), lipoprotein lipase (LPL), and fatty acid oxidation enzymes. This results in increased expression of LPL and reduced expression of apoC-III, leading to enhanced clearance of triglyceride-rich lipoproteins from circulation. Furthermore, fibrates stimulate hepatic fatty acid oxidation, which contributes to decreased hepatic triglyceride synthesis. Collectively, these actions lead to a reduction in serum triglyceride levels and a modest increase in high-density lipoprotein cholesterol (HDL-C) concentrations, thereby improving the overall lipid profile.