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Lipid-lowering agent

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Lipid-lowering agents, also sometimes referred to as hypolipidemic agents, cholesterol-lowering drugs, or antihyperlipidemic agents are a diverse group of pharmaceuticals that are used to lower the level of lipids and lipoproteins, such as cholesterol, in the blood (hyperlipidemia). The American Heart Association recommends the descriptor 'lipid lowering agent' be used for this class of drugs rather than the term 'hypolipidemic'.

Classes

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The several classes of lipid lowering drugs may differ in both their impact on the cholesterol profile and adverse effects. For example, some may lower low density lipoprotein (LDL) levels more so than others, while others may preferentially increase high density lipoprotein (HDL). 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

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  • 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.
  • 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.
  • PCSK9 inhibitors[3][4] are monoclonal antibodies for refractory cases. (e.g. Evolocumab, Inclisiran) They are used in combination with statins.
  • Probucol (withdrawn in several countries)

Alternative

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  • Lecithin has been shown to effectively decrease cholesterol concentration by 33%, lower LDL by 38% and increase HDL by 46%.[5][non-primary source needed]
  • 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.[6] They are associated with a very modest increase in LDL (~5%).
  • Choline
  • Pycnogenol[7]
  • Berberine[8][9]
  • Red yeast rice[10] is the natural source from which statins were discovered, but the FDA currently disallows any RYR with significant amounts of statin to be sold as a dietary supplement [11]
  • Boswellia serrata[12]
  • L-arginine may enhance the effects of a Statin, but will not lead to a reduction in cholesterol alone.[13]
  • Flaxseed oil[14]

Research

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Investigational classes of hypolipidemic agents:

See also

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References

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  1. ^ Alenghat, Francis J.; Davis, Andrew M. (2019). "Management of Blood Cholesterol". JAMA. 321 (8): 800–801. 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. ^ Koren MJ, Scott R, Kim JB et al Lancet 2012; 380:1995-2006
  4. ^ Gugliano RP, Desai NR, Kohli P et al Lancet 2012; 380:2007-17
  5. ^ 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. S2CID 71032494.
  6. ^ "Omega-3 Supplements: In Depth". NCCIH. 2018-05-01. Retrieved 2021-02-02.
  7. ^ Stough, Con K; Pase, Matthew P; Cropley, Vanessa; Myers, Stephen; Nolidin, Karen; King, Rebecca; Camfield, David; Wesnes, Keith; Pipingas, Andrew; Croft, Kevin; Chang, Dennis; Scholey, Andrew B (December 2012). "A randomized controlled trial investigating the effect of Pycnogenol and BacopaCDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: the Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910)". Nutrition Journal. 11 (1): 11. doi:10.1186/1475-2891-11-11. PMC 3310777. PMID 22390677.
  8. ^ Doggrell, SA (May 2005). "Berberine--a novel approach to cholesterol lowering". Expert Opinion on Investigational Drugs. 14 (5): 683–5. doi:10.1517/13543784.14.5.683. PMID 15926873. S2CID 1708378.
  9. ^ Koppen, Laura M.; Whitaker, Andrea; Rosene, Audrey; Beckett, Robert D. (October 2017). "Efficacy of Berberine Alone and in Combination for the Treatment of Hyperlipidemia: A Systematic Review". Journal of Evidence-Based Complementary & Alternative Medicine. 22 (4): 956–968. doi:10.1177/2156587216687695. PMC 5871262. PMID 29228784.
  10. ^ Cicero, Arrigo F. G.; Fogacci, Federica; Zambon, Alberto (9 February 2021). "Red Yeast Rice for Hypercholesterolemia: JACC Focus Seminar". Journal of the American College of Cardiology. 77 (5): 620–628. doi:10.1016/j.jacc.2020.11.056. hdl:11585/827471. ISSN 0735-1097. PMID 33538260. S2CID 231803755.
  11. ^ "Pharmanex Inc. v. Shalala, United States District Court, D. Utah, Central Division Mar 1, 2001 Case No. 2:97CV262K". Casetext. Retrieved 21 June 2019.
  12. ^ Ahangarpour, Akram; Heidari, Hamid; Fatemeh, Ramezani Ali Akbari; Pakmehr, Mostafa; Shahbazian, Hajeye; Ahmadi, Iraj; Mombeini, Zahra; Mehrangiz, Babadi Hajani (2014). "Effect of Boswellia serrata supplementation on blood lipid, hepatic enzymes and fructosamine levels in type2 diabetic patients". Journal of Diabetes and Metabolic Disorders. 13 (1): 29. doi:10.1186/2251-6581-13-29. PMC 3929136. PMID 24495344.
  13. ^ Schulze, Friedrich; Glos, Sabrina; Petruschka, Dörte; Altenburg, Christiane; Maas, Renke; Benndorf, Ralf; Schwedhelm, Edzard; Beil, Ulrich; Böger, Rainer H. (May 2009). "L-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides". Nutrition Research (New York, N.Y.). 29 (5): 291–297. doi:10.1016/j.nutres.2009.04.004. PMID 19555809.
  14. ^ Kristensen, M; Jensen, MG; Aarestrup, J; Petersen, KE; Søndergaard, L; Mikkelsen, MS; Astrup, A (3 February 2012). "Flaxseed dietary fibers lower cholesterol and increase fecal fat excretion, but magnitude of effect depend on food type". Nutrition & Metabolism. 9: 8. doi:10.1186/1743-7075-9-8. PMC 3307491. PMID 22305169.
  15. ^ Pollack, Andrew (29 January 2013) F.D.A. Approves Genetic Drug to Treat Rare Disease The New York Times, Retrieved 31 January 2013
  16. ^ 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
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