Lipid-Lowering Agents 

Updated: Jan 07, 2022
  • Author: Abimbola Farinde, PharmD, PhD; more...
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Lipid-Lowering Agents

HMG-CoA reductase inhibitors (statins)

These agents inhibit the rate-limiting step in cholesterol biosynthesis by competitively inhibiting HMG-CoA reductase. [1, 2, 3] Note the following:

Vitamin B3

Vitamin B3 inhibits very-low-density lipoprotein (VLDL) synthesis. Note the following:

  • LDL reduction of 10%
  • High-density lipoprotein (HDL) increase of 20%
  • Example includes Niacin (nicotinic acid)
  • Contraindications include hypersensitivity, liver disease, active peptic ulcer, severe hypotension, arterial bleeding

Fibrates

Fibrates enhance lipoprotein lipase, resulting in increased VLDL catabolism, fatty acid oxidation, and triglyceride elimination. They decrease hepatic extraction of free fatty acids. Note the following:

2-Azetidiones

These agents inhibit sterol transporter at brush border and, consequently, intestinal absorption of cholesterol.

  • LDL reduction of 15%
  • Example includes Ezetimibe
  • Contraindications include hypersensitivity, coadministration with statins (if active liver disease)

Bile acid sequestrants

These agents lower cholesterol and LDL via bile duct sequestration. Note the following:

  • LDL reduction of 15%
  • Contraindications include biliary/bowel obstruction, serum triglycerides >300-500 mg/dL, history of hypertriglyceridemia-induced pancreatitis

Apolipoprotein B antisense oligonucleotide

These agents target messenger RNA for apolipoprotein B (apoB)–100, the principal apolipoprotein of LDL and its metabolic precursor, VLDL. [5] Note the following:

  • Reduces LDL, ApoB, total cholesterol (TC), and non-HDL cholesterol
  • Example includes Mipomersen
  • Contraindications include hypersensitivity, moderate-to-severe hepatic impairment or active liver disease including persistent increased levels of serum transaminases

MTP inhibitor

These agents directly bind and inhibit microsomal triglyceride transfer protein (MTP), thereby preventing ApoB-containing lipoproteins. Note the following:

  • Reduces LDL, TC, ApoB, and non-HCL cholesterol
  • Example includes Lomitapide [6]
  • Contraindications include pregnancy, coadministration with strong CYP3A4 inhibitors (lomitapide exposure increased 27-fold), moderate-to-severe hepatic impairment or active liver disease including persistent increased levels of serum transaminases

Omega 3 acids

Omega 3 acid agents inhibit acyl CoA:1,2-diacylglycerol acyltransferase. Note the following:

  • Reduces non-HCL cholesterol, ratio of total cholesterol to HDL-C, VLDL, Apo-C, phospholipase A2, and arachidonic acid
  • Contraindications include hypersensitivity or hypersensitivity-related reactions

Small interfering RNA (siRNA) therapy

Inclisiran is a double-stranded small interfering RNA conjugated on sense strand with triantennary N-acetylgalactosamine to facilitate uptake by hepatocytes. In hepatocytes, inclisiran utilizes the RNA interference mechanism and directs catalytic breakdown of mRNA for proprotein convertase subtilisin kexin type 9 (PCSK9). This increases LDL-C receptor recycling and expression on the hepatocyte cell surface, which increases LDL-C uptake and lowers LDL-C levels in the circulation.

  • Reduces LDL-C exceeding 50% over 1-2 years [7]
  • Leqvio (inclisiran) is approved as an adjunct to statins for further reductions of LDL cholesterol levels
  • Side effects: Mild-moderate injection site reaction (eg, pain, redness, rash), joint pain, urinary tract infection, diarrhea, chest cold, pain in legs or arms, and shortness of breath

Combination Drugs

These combination drugs lower lipids:

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