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Combination of | |
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Ezetimibe | via Niemann-Pick C1-Like 1 protein |
Simvastatin | Statin HMG-CoA reductase inhibitor |
Clinical data | |
Pronunciation | /ɛˈzɛtɪmɪbˌsɪmvəˈstætɪn/ |
Trade names | Vytorin (US), Inegy (EU) |
License data | |
Routes of administration | By mouth |
ATC code | |
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Identifiers | |
CAS Number | |
PubChem CID | |
DrugBank | |
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UNII | |
KEGG | |
CompTox Dashboard (EPA) | |
Chemical and physical data | |
Formula | C49H59F2NO8 |
Molar mass | 828.007 g·mol−1 |
3D model (JSmol) | |
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Ezetimibe/simvastatin is a drug combination used for the treatment of dyslipidemia. It is a combination of ezetimibe (known as Zetia in the United States) and the statin drug simvastatin (known as Zocor in the US).
Ezetimibe reduces blood cholesterol by acting at the brush border of the small intestine and inhibiting the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver.
Simvastatin is an HMG-CoA reductase inhibitor or statin. It works by blocking an enzyme that is necessary for the body to make cholesterol. Generic versions were approved in 2017. [2] The combination preparation is marketed by Merck & Co. under the trade names Vytorin in the US and Inegy in the European Union. In 2018, it was the 349th most commonly prescribed medication in the United States, with more than 800 thousand prescriptions. [3]
The combination of ezetimibe and simvastatin treats both sources of cholesterol; absorption in the intestine of both biliary and dietary cholesterol, and production in the liver and peripheral tissues. [4] It is thought that the treatment of high cholesterol from both sources is likely to result in lower cholesterol levels, [4] particularly LDL cholesterol. In a clinical study, it was shown that the combination of ezetimibe and simvastatin was superior to atorvastatin in lowering LDL cholesterol. [5]
Published in 2015, the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) randomized 18,144 patients with ACS to simvastatin 40 mg/d plus ezetimibe 10 mg/d or simvastatin alone. With median follow-up of 6 years, simvastatin+ezetimibe was found to reduce the primary outcome of CV mortality, major CV event, or nonfatal stroke (34.7% vs. 32.7%; P=0.016; NNT 50 per 7 years or NNT 350 per 1 year ). There was no reduction in all-cause or CV mortality with simvastatin+ezetimibe, though there was a reduction in MI and stroke. [6]
The two-year ENHANCE Study [7] failed to provide evidence that ezetimibe/simvastatin was better than simvastatin (a generic medication) in terms of achieving a lower change from baseline in carotid intima-media thickness despite lower LDL levels in a population of patients with heterozygous familial hypercholesterolemia (a form of high cholesterol that affects less than 1% of patients). Clinical events such as heart attack and stroke were not measured as primary or secondary endpoints of the study making it impossible to determine Vytorin's effect on these events. [8] [ medical citation needed ]
The American College of Cardiology released a statement suggesting that "major clinical decisions not be made on the basis of the ENHANCE study alone", given the small and unique patient population, 720 patients in an Amsterdam hospital with heterozygous familial hypercholesterolemia. [9]
Merck and Schering Plough have reported that they have three trials underway to focus on outcomes, measuring the drug's effect on heart attacks and strokes in patients. [8]
These results were presented in full at the American College of Cardiology meeting on 30 March 2008, two years after the last patient completed the study. [10] The House Committee on Energy and Commerce conducted an inquiry into the delayed disclosure of the study data.[ citation needed ]
In the United States, Vytorin featured a television advertising campaign showing a series of split-screen images of a person and a food item to make the point that cholesterol comes from two sources and can be absorbed from food or manufactured by the body, and that heredity plays a role in the latter. [11] This point is a departure from the commonly held belief that high cholesterol only comes from the food that you eat. [12] In each commercial, the person's features or clothing and the food plated to emphasize the resemblance between the person and the food. For example, in one advertisement a woman wearing a yellow shirt and a pin is juxtaposed with a similarly colored piece of pie.
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, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL is involved in atherosclerosis, a process in which it is oxidized within the walls of arteries.
Statins are a class of medications that reduce illness and mortality in people who are at high risk of cardiovascular disease. They are the most commonly prescribed cholesterol-lowering drugs, and are also known as HMG-CoA reductase inhibitors.
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'.
Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD), which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.
Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth.
Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of heart problems in those at high risk. It is taken by mouth.
Fluvastatin is a member of the statin drug class, used to treat hypercholesterolemia and to prevent cardiovascular disease.
Rosuvastatin, sold under the brand name Crestor among others, is a statin medication, used to prevent cardiovascular disease in those at high risk and treat abnormal lipids. It is recommended to be used together with dietary changes, exercise, and weight loss. It is taken orally.
Pravastatin, sold under the brand name Pravachol among others, is a statin medication, used for preventing cardiovascular disease in those at high risk and treating abnormal lipids. It is suggested to be used together with diet changes, exercise, and weight loss. It is taken by mouth.
Ezetimibe 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 than a statin. It is taken by mouth. It is also available in the fixed combinations ezetimibe/simvastatin, ezetimibe/atorvastatin, ezetimibe/rosuvastatin, and ezetimibe/bempedoic acid.
Pitavastatin is a member of the blood cholesterol lowering medication class of statins.
Cholesterol absorption inhibitors are a class of compounds that prevent the uptake of cholesterol from the small intestine into the circulatory system. Most of these molecules are monobactams but show no antibiotic activity. An example is ezetimibe Another example is Sch-48461. The "Sch" is for Schering-Plough, where these compounds were developed. Phytosterols are also cholesterol absorption inhibitors.
Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol, in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH. Nevertheless, treatment is usually effective.
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 clinical trials as single treatment and in combinations with atorvastatin, ezetimibe and fenofibrate.
Sitagliptin/simvastatin, sold under the brand name Juvisync, is a fixed-dose combination anti-diabetic medication used to treat type 2 diabetes and hypercholesterolemia. It contains sitagliptin and simvastatin. Sitagliptin is a dipeptidyl peptidase-4 inhibitor and simvastatin is an HMG-CoA reductase inhibitor. These two disorders commonly occur in people at the same time, and have been typically treated with administration of these medications separately. The combination was approved in 2011, and sold under the brand name Juvisync by Merck. Juvisync was later removed from the market in 2013, due to business reasons.
Ezetimibe/atorvastatin is a cholesterol lowering combination drug. In the United States, it was approved in May 2013, by the Food and Drug Administration for the treatment of elevated low-density lipoprotein (LDL) in patients with primary or mixed hyperlipidemia as adjunctive therapy to diet. It has also been approved to reduce elevated total cholesterol and elevated LDL in patients diagnosed with homozygous familial hypercholesterolemia as an adjunctive treatment to other hyperlipidemia treatments.
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, and heterozygous familial hypercholesterolemia (HeFH). It is a small interfering RNA (siRNA) that acts as an inhibitor of a proprotein convertase, specifically, inhibiting translation of the protein PCSK9.
Bempedoic acid, sold under the brand name Nexletol among others, is a medication for the treatment of hypercholesterolemia.
Ezetimibe/rosuvastatin, sold under the brand name Ridutrin among others, is a combination medication used to treat high cholesterol. In some countries it is sold as a kit or a pack containing two distinct pills.
Bempedoic acid/ezetimibe, sold under the brand name Nexlizet among others, is a fixed-dose combination medication used for the treatment of high cholesterol. It is a combination of bempedoic acid and ezetimibe.