Simvastatin

Generic Name
Simvastatin
Brand Names
Cholib, FloLipid, Simcor, Vytorin, Zocor
Drug Type
Small Molecule
Chemical Formula
C25H38O5
CAS Number
79902-63-9
Unique Ingredient Identifier
AGG2FN16EV
Background

Simvastatin, also known as the brand name product Zocor, is a lipid-lowering drug derived synthetically from a fermentation product of Aspergillus terreus. It belongs to the statin class of medications, which are used to lower the risk of cardiovascular disease and manage abnormal lipid levels by inhibiting the endogenous production of cholesterol in the liver. More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase, which catalyzes the conversion of HMG-CoA to mevalonic acid and is the third step in a sequence of metabolic reactions involved in the production of several compounds involved in lipid metabolism and transport including cholesterol, low-density lipoprotein (LDL) (sometimes referred to as "bad cholesterol"), and very low-density lipoprotein (VLDL). Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD, such as those with Type 2 Diabetes. The clear evidence of the benefit of statin use coupled with very minimal side effects or long term effects has resulted in this class becoming one of the most widely prescribed medications in North America.

Simvastatin and other drugs from the statin class of medications including atorvastatin, pravastatin, rosuvastatin, fluvastatin, and lovastatin are considered first-line options for the treatment of dyslipidemia. Increasing use of the statin class of drugs is largely due to the fact that cardiovascular disease (CVD), which includes heart attack, atherosclerosis, angina, peripheral artery disease, and stroke, has become a leading cause of death in high-income countries and a major cause of morbidity around the world. Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD. Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality. Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack. Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.

While all statin medications are considered equally effective from a clinical standpoint, rosuvastatin is considered the most potent; doses of 10 to 40mg rosuvastatin per day were found in clinical studies to result in a 45.8% to 54.6% decrease in LDL cholesterol levels, while simvastatin has been found to have an average decrease in LDL-C of ~35%. Potency is thought to correlate to tissue permeability as the more lipophilic statins such as simvastatin are thought to enter endothelial cells by passive diffusion, as opposed to hydrophilic statins such as pravastatin and rosuvastatin which are taken up into hepatocytes through OATP1B1 (organic anion transporter protein 1B1)-mediated transport. Despite these differences in potency, several trials have demonstrated only minimal differences in terms of clinical outcomes between statins.

Indication

Simvastatin is indicated for the treatment of hyperlipidemia to reduce elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL‑C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C).

This includes the treatment of primary hyperlipidemia (Fredrickson type IIa, heterozygous familial and nonfamilial), mixed dyslipidemia (Fredrickson type IIb), hypertriglyceridemia (Fredrickson type IV hyperlipidemia), primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia), homozygous familial hypercholesterolemia (HoFH) as an adjunct to other lipid-lowering treatments, as well as adolescent patients with Heterozygous Familial Hypercholesterolemia (HeFH).

Simvastatin is also indicated to reduce the risk of cardiovascular morbidity and mortality including myocardial infarction, stroke, and the need for revascularization procedures. It is primarily used in patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease.

Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD. Statin-indicated conditions include diabetes mellitus, clinical atherosclerosis (including myocardial infarction, acute coronary syndromes, stable angina, documented coronary artery disease, stroke, trans ischemic attack (TIA), documented carotid disease, peripheral artery disease, and claudication), abdominal aortic aneurysm, chronic kidney disease, and severely elevated LDL-C levels.

Associated Conditions
Cardiovascular Events, Diabetes Mellitus, Heterozygous Familial Hypercholesterolemia (HeFH), High Cholesterol, Homozygous Familial Hypercholesterolaemia (HoFH), Mixed Hyperlipidemia, History of coronary heart disease cardiovascular event, History of stroke or other cerebrovascular disease cardiovascular event
Associated Therapies
-

Ezetimibe Plus Simvastatin Versus Simvastatin Alone in African-American Subjects With Primary Hypercholesterolemia (P03377)

First Posted Date
2008-04-02
Last Posted Date
2024-08-15
Lead Sponsor
Organon and Co
Target Recruit Count
247
Registration Number
NCT00650663

Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis

First Posted Date
2008-03-31
Last Posted Date
2019-12-12
Lead Sponsor
Imperial College London
Target Recruit Count
140
Registration Number
NCT00647348
Locations
🇬🇧

MRI Unit, National Society for Epilepsy, Chesham Lane, Chalfont St. Peter, Buckinghamshire, United Kingdom

🇬🇧

Charing Cross Hospital, Fulham Palace Road, Hammersmith, London, United Kingdom

🇬🇧

Brighton & Sussex University Hospitals NHS Trust, Eastern Road, Brighton, United Kingdom

Add-on Simvastatin in Schizophrenia Trial

Not Applicable
Terminated
Conditions
Interventions
First Posted Date
2008-02-01
Last Posted Date
2017-03-24
Lead Sponsor
New York State Psychiatric Institute
Target Recruit Count
15
Registration Number
NCT00605995
Locations
🇮🇱

Sheba Medical Center, Ramat Gan, Israel

Efficacy and Safety of Simvastatin in the Treatment of Portal Hypertension

Phase 2
Completed
Conditions
Interventions
First Posted Date
2008-01-15
Last Posted Date
2008-01-15
Lead Sponsor
Hospital Clinic of Barcelona
Target Recruit Count
59
Registration Number
NCT00594191
Locations
🇪🇸

Servicio de Gastroenterología, Hospital Ramón y Cajal, Madrid, Spain

🇪🇸

Hepatic Hemodynamic Laboratory. Liver Unit. Hospital Clinic., Barcelona, Spain

🇪🇸

Servicio de Gastroenterología, Hospital Universitario General Gregorio Marañón, Madrid, Spain

Effect of Acute Statin Treatment in Patients Undergoing Percutaneous Coronary Intervention

Not Applicable
Terminated
Conditions
Interventions
First Posted Date
2008-01-08
Last Posted Date
2012-11-08
Lead Sponsor
Mayo Clinic
Target Recruit Count
57
Registration Number
NCT00588471
Locations
🇺🇸

Mayo Clinic, Rochester, Minnesota, United States

Comprehensive Magnetic Resonance of Peripheral Arterial Disease

First Posted Date
2008-01-07
Last Posted Date
2017-08-21
Lead Sponsor
University of Virginia
Target Recruit Count
85
Registration Number
NCT00587678
Locations
🇺🇸

University of Virgina Health System, Charlottesville, Virginia, United States

The Acute Effect of Statins on Inflammatory Markers of Athersclerotic Tissue

Not Applicable
Completed
Conditions
Interventions
First Posted Date
2008-01-07
Last Posted Date
2023-12-12
Lead Sponsor
Mayo Clinic
Target Recruit Count
35
Registration Number
NCT00587717

Effects of Simvastatin on Biochemical Parameters and Outcome of IVF-ICSI in Pcos Patients

Phase 3
Completed
Conditions
Interventions
First Posted Date
2007-12-18
Last Posted Date
2009-07-02
Lead Sponsor
Tehran University of Medical Sciences
Target Recruit Count
120
Registration Number
NCT00575601
Locations
🇮🇷

Imam Khomeiny Hospital, Tehran, Iran, Islamic Republic of

Simvastatin in Waldenstrom's Macroglobulinemia

Phase 2
Terminated
Conditions
Interventions
First Posted Date
2007-12-18
Last Posted Date
2015-12-16
Lead Sponsor
Dana-Farber Cancer Institute
Target Recruit Count
18
Registration Number
NCT00575965
Locations
🇺🇸

Dana-Farber Cancer Institute, Boston, Massachusetts, United States

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