Lipid-lowering agent

Hypolipidemic agents, cholesterol-lowering drugs or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of high levels of fats (lipids), such as cholesterol, in the blood (hyperlipidemia). They are called lipid-lowering drugs. These are drugs which lower the level of lipids and lipoproteins in blood.

Classes

The several classes of hypolipidemic drugs may differ in both their impact on the cholesterol profile and adverse effects. For example, some may lower the "bad cholesterol" low density lipoprotein (LDL) more so than others, while others may preferentially increase high density lipoprotein (HDL), "the good cholesterol". Clinically, the choice of an agent depends on the patient's cholesterol profile, cardiovascular risk, and the liver and kidney functions of the patient, evaluated against the balancing of risks and benefits of the medications. In the United States, this is guided by the evidence-based guideline most recently updated in 2018 by the American College of Cardiology & American Heart Association. [1]

Established
  • Statins (HMG-CoA reductase inhibitors) are particularly well suited for lowering LDL, the cholesterol with the strongest links to vascular diseases. In studies using standard doses, statins have been found to lower LDL-C by 18% to 55%, depending on the specific statin being used. A risk exists of muscle damage (myopathy and rhabdomyolysis) with statins. Hypercholesterolemia is not a risk factor for mortality in persons older than 70 years and risks from statin drugs are more increased after age 85.[2]
  • Fibrates are indicated for hypertriglyceridemia. Fibrates typically lower triglycerides by 20% to 50%. Level of the good cholesterol HDL is also increased. Fibrates may decrease LDL, though generally to a lesser degree than statins. Similar to statins, the risk of muscle damage exists.
  • Niacin, like fibrates, is also well suited for lowering triglycerides by 20–50%. It may also lower LDL by 5–25% and increase HDL by 15–35%. Niacin may cause hyperglycemia and may also cause liver damage. The niacin derivative acipimox is also associated with a modest decrease in LDL.
  • Lecithin has been shown to effectively decrease cholesterol concentration by 33%, lower LDL by 38% and increase HDL by 46%. [3]
  • Bile acid sequestrants (resins, e.g. cholestyramine) are particularly effective for lowering LDL-C by sequestering the cholesterol-containing bile acids released into the intestine and preventing their reabsorption from the intestine. It decreases LDL by 15–30% and raises HDL by 3–5%, with little effect on triglycerides, but can cause a slight increase. Bile acid sequestrants may cause gastrointestinal problems and may also reduce the absorption of other drugs and vitamins from the gut.
  • Ezetimibe is a selective inhibitor of dietary cholesterol absorption.
  • Lomitapide is a microsomal triglyceride transfer protein inhibitor.
  • Phytosterols may be found naturally in plants. Similar to ezetimibe, phytosterols reduce the absorption of cholesterol in the gut, so they are most effective when consumed with meals. However, their precise mechanism of action differs from ezetimibe.
  • Omega-3 supplements taken at high doses can reduce levels of triglycerides.[4] They are associated with a very modest increase in LDL (~5%).
  • PCSK9 inhibitors[5][6] are monoclonal antibodies for refractory cases. They are used in combination with statins.

Research

Investigational classes of hypolipidemic agents:

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References
  1. Alenghat, Francis J.; Davis, Andrew M. (2019). "Management of Blood Cholesterol". JAMA. 321: 800. doi:10.1001/jama.2019.0015. ISSN 0098-7484. PMC 6679800. PMID 30715135.
  2. AMDA – The Society for Post-Acute and Long-Term Care Medicine (February 2014), "Ten Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation, AMDA – The Society for Post-Acute and Long-Term Care Medicine, retrieved 20 April 2015.
  3. Wójcicki, J.; Pawlik, A.; Samochowiec, L.; Kaldo??Ska, M.; Myśliwiec, Z. (1995). "Clinical evaluation of lecithin as a lipid-lowering agent". Phytotherapy Research. 9 (8): 597–599. doi:10.1002/ptr.2650090814.
  4. "Omega-3 Supplements: In Depth". NCCIH. 2009-07-01. Retrieved 2019-08-12.
  5. Koren MJ, Scott R, Kim JB et al Lancet 2012; 380:1995-2006
  6. Gugliano RP, Desai NR, Kohli P et al Lancet 2012; 380:2007-17
  7. Pollack, Andrew (29 January 2013) F.D.A. Approves Genetic Drug to Treat Rare Disease The New York Times, Retrieved 31 January 2013
  8. Staff (29 January 2013) FDA approves new orphan drug Kynamro to treat inherited cholesterol disorder U.S. Food and Drug Administration, Retrieved 31 January 2013

See also
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