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
-

Pharmacodynamic Drug Interaction Between Cilostazol and Statins

Phase 1
Completed
Conditions
Interventions
First Posted Date
2013-06-06
Last Posted Date
2015-05-27
Lead Sponsor
Samsung Medical Center
Target Recruit Count
63
Registration Number
NCT01870466
Locations
🇰🇷

Samsung Medical Center, Seoul, Korea, Republic of

Efficacy Study of SIMVASTATIN to Treat Chronic Rhinosinusitis After Failure of Optimal Treatment

Phase 2
Terminated
Conditions
Interventions
First Posted Date
2013-01-18
Last Posted Date
2015-07-13
Lead Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
Target Recruit Count
7
Registration Number
NCT01771198
Locations
🇨🇦

Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada

Permeability MRI in Cerebral Cavernous Malformations Type 1 in New Mexico: Effects of Statins

First Posted Date
2013-01-09
Last Posted Date
2024-03-12
Lead Sponsor
University of New Mexico
Target Recruit Count
12
Registration Number
NCT01764451
Locations
🇺🇸

University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States

LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-2

First Posted Date
2013-01-09
Last Posted Date
2022-11-08
Lead Sponsor
Amgen
Target Recruit Count
2067
Registration Number
NCT01763866
Locations
🇬🇧

Research Site, Whitby, United Kingdom

Assess the Pharmacokinetics of Rosuvastatin and Simvastatin When Administered Alone or in Combination With Fostamatinib

First Posted Date
2012-11-12
Last Posted Date
2013-02-04
Lead Sponsor
AstraZeneca
Target Recruit Count
42
Registration Number
NCT01725230
Locations
🇺🇸

Research Site, Overland Park, Kansas, United States

Effect of Simvastatin Treatment on Vaso-occlusive Pain in Sickle Cell Disease

Phase 1
Completed
Conditions
Interventions
First Posted Date
2012-10-08
Last Posted Date
2016-12-19
Lead Sponsor
UCSF Benioff Children's Hospital Oakland
Target Recruit Count
24
Registration Number
NCT01702246
Locations
🇺🇸

Children's Hospital and Research Center Oakland, Oakland, California, United States

A Pharmacokinetic Interaction Study Between TMC435, Atorvastatin and Simvastatin in Healthy Participants

First Posted Date
2012-09-21
Last Posted Date
2013-03-04
Lead Sponsor
Janssen Research & Development, LLC
Target Recruit Count
36
Registration Number
NCT01689623

The Effect of XueZhiKang on Fatigue:Comparing With Simvastatin

Phase 4
Completed
Conditions
Interventions
First Posted Date
2012-09-18
Last Posted Date
2014-05-19
Lead Sponsor
Wenzhou Medical University
Target Recruit Count
60
Registration Number
NCT01686451
Locations
🇨🇳

Second Hispital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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