Lipid-lowering agents, also sometimes referred to as hypolipidemic agents, cholesterol-lowering drugs, or antihyperlipidemic agents are a diverse group of

pharmaceuticals Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...

that are used to lower the level of lipids and lipoproteins, such as cholesterol, in the blood (

hyperlipidemia Hyperlipidemia is abnormally high levels of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also use ...

). 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 Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

(LDL) levels more so than others, while others may preferentially increase

high density lipoprotein High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...

(HDL). Clinically, the choice of an agent depends on the patient's cholesterol profile
cardiovascular risk
and the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

and

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

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 Evidence-based practice is the idea that occupational practices ought to be based on scientific evidence. The movement towards evidence-based practices attempts to encourage and, in some instances, require professionals and other decision-makers ...

guideline most recently updated in 2018 by the

American College of Cardiology The American College of Cardiology (ACC), based in Washington, D.C., is a nonprofit medical association established in 1949. It bestows credentials upon cardiovascular specialists who meet its qualifications. Education is a core component of the ...

American Heart Association The American Heart Association (AHA) is a nonprofit organization in the United States that funds cardiovascular medical research, educates consumers on healthy living and fosters appropriate Heart, cardiac care in an effort to reduce disability ...

Established

Statin Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

s (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 In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. ''Myopathy'' means muscle disease ( Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meaning implies that the primary defec ...

and

rhabdomyolysis Rhabdomyolysis (shortened as rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some o ...

) 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. *

Fibrate In pharmacology, the fibrates are a class of amphipathic carboxylic acids and esters. They are derivatives of fibric acid (phenoxyisobutyric acid). They are used for a range of metabolic disorders, mainly hypercholesterolemia (high choles ...

s are indicated for

hypertriglyceridemia Hypertriglyceridemia is the presence of high amounts of triglycerides in the blood. Triglycerides are the most abundant fatty molecule in most organisms. Hypertriglyceridemia occurs in various physiologic conditions and in various diseases, and ...

. 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. *

Nicotinic acid Nicotinic acid, or niacin, is an organic compound and a vitamer of vitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan. Nicotinic acid is also a prescription medication. Amounts f ...

, 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 Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating. Blood gluc ...

and may also cause

liver damage Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground glas ...

. The niacin derivative

acipimox Acipimox (trade name Olbetam in Europe) is a niacin derivative used as a lipid-lowering agent. It reduces triglyceride levels and increases HDL cholesterol. It may have less marked adverse effects than niacin, although it is unclear whether the r ...

is also associated with a modest decrease in LDL. Introduced in 1955. *

Bile acid sequestrant The bile acid sequestrants are a group of resins used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by combining with bile constituents and preventing their reabsorption f ...

s (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 Ezetimibe, sold under the brand name Zetia among others, is a medication used to treat high blood cholesterol and certain other lipid abnormalities. Generally it is used together with dietary changes and a statin. Alone, it is less preferred ...

is a selective inhibitor of dietary cholesterol absorption. *

Lomitapide Lomitapide , sold under the brand name Juxtapid in the US and Lojuxta in the EU, is a medication used as a lipid-lowering agent for the treatment of familial hypercholesterolemia, developed by Aegerion Pharmaceuticals. It has been tested in cli ...

is a

microsomal triglyceride transfer protein Microsomal triglyceride transfer protein large subunit is a protein that in humans is encoded by the ''MTTP'', also known as ''MTP'', gene. ''MTTP'' encodes the large subunit of the heterodimeric microsomal triglyceride transfer protein (MTP). ...

inhibitor. *

PCSK9 Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the ''PCSK9'' gene in humans on chromosome 1. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. Similar genes ( orth ...

inhibitors are

monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a Lineage (evolution), cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Mon ...

for refractory cases. (e.g.

Evolocumab Evolocumab, sold under the brand name Repatha, is a monoclonal antibody that is an immunotherapy medication for the treatment of hyperlipidemia. Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/ke ...

Inclisiran Inclisiran, sold under the brand name Leqvio, is a medication used for the treatment of high low-density lipoprotein (LDL) cholesterol and for the treatment of people with atherosclerotic cardiovascular disease (ASCVD), ASCVD risk-equivalents, ...

) They are used in combination with

statin Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

s. *

Probucol Probucol, sold under the trade name Lorelco among others, is an lipid-lowering agent initially developed for the treatment of coronary artery disease. Clinical use was discontinued in some countries after it was found that the drug may have the ...

decreases LDL independently of the LDL receptor, and decreases HDL-C by enhancing its liver receptor and reducing ABCA1-dependent transport. The reduction of HDL-C, combined with early uncertainties around its mechanism of action, has historically lead to its discontinuation and replacement by statins in Western countries. However, instead of lowering

reverse cholesterol transport Reverse cholesterol transport (RCT) is a multistep process comprising removal of excess cholesterol from cells in the body and delivery to the liver for excretion into the small intestine. Enhancing reverse cholesterol transport is considered a po ...

by HDL particles, probucol seems to increase it. Introduced in the 1970s. It predated the statins by about a decade.

Alternative

Lecithin Lecithin ( ; from the Ancient Greek "yolk") is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues which are amphiphilic – they attract both water and fatty substances (and so ar ...

has been shown to effectively decrease cholesterol concentration by 33%, lower LDL by 38% and increase HDL by 46%. *

Phytosterol Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanol ester, stanols. More than 250 sterols and related compounds have been identified ...

s 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 Omega−3 fatty acids, also called omega−3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their ...

supplements taken at high doses can reduce levels of triglycerides. They are associated with a very modest increase in LDL (~5%). *

Choline Choline is a cation with the chemical formula . Choline forms various Salt (chemistry), salts, such as choline chloride and choline bitartrate. An essential nutrient for animals, it is a structural component of phospholipids and cell membrane ...

Pycnogenol Maritime pine bark extract is an extract from the bark of ''Pinus pinaster'' which is used as a dietary supplement. It is composed mostly of proanthocyanidins. Pycnogenol is a trademarked name for a standardized preparation that contains 70% pr ...

Berberine Berberine is a Quaternary ammonium cation, quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids, occurring naturally as a secondary metabolite in some plants including species of ''Berberis'', from which its name ...

Red yeast rice Red yeast rice or red rice ''koji'' is a bright reddish purple fermented rice, which acquires its color from being cultivated with the mold '' Monascus purpureus''. Red yeast rice is what is referred to as a '' kōji'' in Japanese, meaning "gr ...

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 *

Boswellia serrata ''Boswellia serrata'' is a plant that produces Indian frankincense. The plant is native to much of India and the Punjab region that extends into Pakistan. Sustainability ''Boswellia serrata'' is currently at risk of being eradicated because of n ...

L-arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the ...

may enhance the effects of a Statin, but will not lead to a reduction in cholesterol alone. *

Flaxseed oil Linseed oil, also known as flaxseed oil or flax oil (in its edible form), is a colorless to yellowish oil obtained from the dried, ripened seeds of the flax plant (''Linum usitatissimum''). The oil is obtained by pressing, sometimes followed by ...

Research

Investigational classes of hypolipidemic agents: *

CETP inhibitor A CETP inhibitor is a member of a class of drugs that inhibit cholesterylester transfer protein (CETP). They are intended to reduce the risk of atherosclerosis (a cardiovascular disease) by improving blood lipid levels. At least three medications ...

s (cholesteryl ester transfer protein), 1 candidate is in trials. (

Anacetrapib Anacetrapib is a CETP inhibitor which was being developed to treat elevated cholesterol levels in an effort to prevent cardiovascular disease. In 2017 its development was abandoned by Merck. Evidence In 2017 REVEAL trial anacetrapib was shown t ...

) It is expected that these drugs will mainly increase HDL while lowering LDL * Squalene synthase inhibitor *

ApoA-1 Milano Apolipoprotein A-I Milano (also ETC-216, now MDCO-216) is a naturally occurring genetic mutation, mutated variant of the apolipoprotein A1 protein found in human high density lipoprotein, HDL, the lipoprotein particle that carries cholesterol from ...

* Succinobucol (AGI-1067), a novel antioxidant, failed a phase-III trial. * Apoprotein-B inhibitor

mipomersen Mipomersen (International Nonproprietary Name, INN; trade name Kynamro) is a drug used to treat homozygous familial hypercholesterolemia and is administered by subcutaneous injection. There is a serious risk of liver damage from this drug and it ...

(approved by the FDA in 2013 homozygous

familial hypercholesterolemia Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol (LDL cholesterol), in the blood and early cardiovascular diseases. The mos ...

.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). * Bempedoic acid, an ATP citrate lyase inhibitor

References

{{Authority control Hypolipidemic agents

Classes

Established

Alternative

Research

See also

References