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
-

Clinical Trial of Simvastatin to Treat Generalized Vitiligo

Phase 2
Completed
Conditions
Interventions
First Posted Date
2012-01-25
Last Posted Date
2018-11-14
Lead Sponsor
John Harris
Target Recruit Count
15
Registration Number
NCT01517893
Locations
🇺🇸

University of Massachusetts Medical School Clinical Research Center, Worcester, Massachusetts, United States

A Prevention Trial in Subjects at High Risk for Breast Cancer

First Posted Date
2011-12-28
Last Posted Date
2014-06-18
Lead Sponsor
European Institute of Oncology
Target Recruit Count
150
Registration Number
NCT01500577
Locations
🇮🇹

European Institute of Oncology, Milan, Italy

The Effect of Multiple Doses of Epanova® on the Multiple-Dose Pharmacokinetics of Simvastatin in Healthy Normal Subjects

First Posted Date
2011-12-06
Last Posted Date
2015-04-30
Lead Sponsor
AstraZeneca
Target Recruit Count
52
Registration Number
NCT01486433

A Study To Estimate The Effect Of Repeated Dosing of PF-05175157 On The Pharmacokinetics Of A Single Dose Of Simvastatin In Healthy Adult Subjects

Phase 1
Completed
Conditions
Interventions
First Posted Date
2011-11-10
Last Posted Date
2018-11-14
Lead Sponsor
Pfizer
Target Recruit Count
14
Registration Number
NCT01469468
Locations
🇺🇸

Pfizer Investigational Site, South Miami, Florida, United States

Endothelial Facilitation in Alzheimer's Disease

First Posted Date
2011-09-23
Last Posted Date
2019-07-30
Lead Sponsor
University of Massachusetts, Worcester
Target Recruit Count
11
Registration Number
NCT01439555
Locations
🇺🇸

UMass Medical School/ UMass Memorial Medical Center, Worcester, Massachusetts, United States

SLOS: The Effect of Simvastatin in Patients Receiving Cholesterol Supplementation

Not Applicable
Terminated
Conditions
Interventions
First Posted Date
2011-09-15
Last Posted Date
2019-10-01
Lead Sponsor
Oregon Health and Science University
Target Recruit Count
1
Registration Number
NCT01434745
Locations
🇺🇸

Oregon Health and Science University, Portland, Oregon, United States

Effect of Ezetimibe or Simvastatin or Both on Low Densitiy Lipoprotein -Subfractions in Patients With Type 2 Diabetes

First Posted Date
2011-06-28
Last Posted Date
2012-06-19
Lead Sponsor
University Hospital Freiburg
Target Recruit Count
41
Registration Number
NCT01384058
Locations
🇩🇪

Institut für Stoffwechselforschung, Frankfurt, Germany

🇩🇪

Stephan Jacob, MD, Villingen-.Schwenningen, Germany

Microcirculation In Acute Coronary Syndromes

First Posted Date
2011-06-27
Last Posted Date
2020-10-22
Lead Sponsor
Helse Stavanger HF
Target Recruit Count
25
Registration Number
NCT01382472
Locations
🇳🇴

Stavanger University Hospital, Stavanger, Norway

🇳🇴

University Hospital of North Norway, Tromsø, Norway

🇳🇴

St. Olavs Hospital, Trondheim, Norway

Simvastatin Treatment of Pachyonychia Congenita

Not Applicable
Conditions
First Posted Date
2011-06-27
Last Posted Date
2011-06-27
Lead Sponsor
Tel-Aviv Sourasky Medical Center
Target Recruit Count
10
Registration Number
NCT01382511

Protocol for Correlating Enteropathic Severity and Small Intestinal CYP3A4 Activity in Patients With Celiac Disease

Phase 2
Completed
Conditions
First Posted Date
2011-04-19
Last Posted Date
2011-12-13
Lead Sponsor
All India Institute of Medical Sciences, New Delhi
Target Recruit Count
41
Registration Number
NCT01338324
Locations
🇮🇳

All India Institute of Medical Sciences, New Delhi, Delhi, India

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