Lipid-lowering agent explained

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

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

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

Lecithin has been shown to effectively decrease cholesterol concentration by 33%, lower LDL by 38% and increase HDL by 46%.^[5]
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

Investigational classes of hypolipidemic agents:

CETP inhibitors (cholesteryl ester transfer protein), 1 candidate is in trials. (Anacetrapib) It is expected that these drugs will mainly increase HDL while lowering LDL
Squalene synthase inhibitor
ApoA-1 Milano
Succinobucol (AGI-1067), a novel antioxidant, failed a phase-III trial.
Apoprotein-B inhibitor mipomersen (approved by the FDA in 2013 homozygous familial hypercholesterolemia.^[15] ^[16]).
Bempedoic acid, an ATP citrate lyase inhibitor

Notes and References

Alenghat. Francis J.. Davis. Andrew M.. Management of Blood Cholesterol. JAMA. 2019. 0098-7484. 10.1001/jama.2019.0015. 30715135. 321. 8. 800–801. 6679800.
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Koren MJ, Scott R, Kim JB et al Lancet 2012; 380:1995-2006
Gugliano RP, Desai NR, Kohli P et al Lancet 2012; 380:2007-17
10.1002/ptr.2650090814. Clinical evaluation of lecithin as a lipid-lowering agent. Phytotherapy Research. 9. 8. 597–599. 1995. Wójcicki. J.. Pawlik. A.. Samochowiec. L.. Kaldo??Ska. M.. Myśliwiec. Z.. 71032494.
Web site: Omega-3 Supplements: In Depth. 2018-05-01. NCCIH. en. 2021-02-02.
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 . 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 . December 2012 . 11 . 1 . 11 . 10.1186/1475-2891-11-11. 22390677 . 3310777 . free .
Doggrell . SA . Berberine--a novel approach to cholesterol lowering. . Expert Opinion on Investigational Drugs . May 2005 . 14 . 5 . 683–5 . 10.1517/13543784.14.5.683 . 15926873 . 1708378 .
Koppen . Laura M. . Whitaker . Andrea . Rosene . Audrey . Beckett . Robert D. . Efficacy of Berberine Alone and in Combination for the Treatment of Hyperlipidemia: A Systematic Review . Journal of Evidence-Based Complementary & Alternative Medicine . October 2017 . 22 . 4 . 956–968 . 10.1177/2156587216687695 . 29228784 . 5871262 . en.
Cicero . Arrigo F. G. . Fogacci . Federica . Zambon . Alberto . Red Yeast Rice for Hypercholesterolemia: JACC Focus Seminar . Journal of the American College of Cardiology . 9 February 2021 . 77 . 5 . 620–628 . 10.1016/j.jacc.2020.11.056 . 33538260 . 231803755 . en . 0735-1097. 11585/827471 . free .
Web site: Pharmanex Inc. v. Shalala, United States District Court, D. Utah, Central Division Mar 1, 2001 Case No. 2:97CV262K . Casetext . 21 June 2019.
Ahangarpour . Akram . Heidari . Hamid . Fatemeh . Ramezani Ali Akbari . Pakmehr . Mostafa . Shahbazian . Hajeye . Ahmadi . Iraj . Mombeini . Zahra . Mehrangiz . Babadi Hajani . Effect of Boswellia serrata supplementation on blood lipid, hepatic enzymes and fructosamine levels in type2 diabetic patients . Journal of Diabetes and Metabolic Disorders . 2014 . 13 . 1 . 29 . 10.1186/2251-6581-13-29 . 24495344 . 3929136 . en . free .
Schulze . Friedrich . Glos . Sabrina . Petruschka . Dörte . Altenburg . Christiane . Maas . Renke . Benndorf . Ralf . Schwedhelm . Edzard . Beil . Ulrich . Böger . Rainer H. . L-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides . Nutrition Research (New York, N.Y.) . 291–297 . 10.1016/j.nutres.2009.04.004 . May 2009. 29 . 5 . 19555809 .
Kristensen . M . Jensen . MG . Aarestrup . J . Petersen . KE . Søndergaard . L . Mikkelsen . MS . Astrup . A . Flaxseed dietary fibers lower cholesterol and increase fecal fat excretion, but magnitude of effect depend on food type. . Nutrition & Metabolism . 3 February 2012 . 9 . 8 . 10.1186/1743-7075-9-8 . 22305169 . 3307491 . free .
Pollack, Andrew (29 January 2013) F.D.A. Approves Genetic Drug to Treat Rare Disease The New York Times, Retrieved 31 January 2013
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