This page shows what was measured, who it was measured in, and what that does not settle.
What Simvastatin does in the body
High cholesterol, and the prevention of heart attacks and strokes in people who already have vascular disease or diabetes
Most of the cholesterol in your blood is not eaten, it is manufactured, mostly by the liver, and simvastatin blocks the slowest step in that assembly line. Starved of the cholesterol it used to make, the liver cell responds by putting more LDL receptors on its surface — hooks that pull cholesterol-carrying particles out of the bloodstream. The blood level falls because the liver is now removing LDL faster, not because anything was blocked in the artery. The tablet you swallow is not the active drug: it is a closed-ring form that has to be opened by the body into simvastatin acid before it inhibits anything.
What happened in people
All-cause mortality 8% against 12% over a median 5.4 years in 4,444 patients with coronary disease (4S; RR 0.70, 95% CI 0.58 to 0.85, p=0.0003)
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
That carotid intima-media thickness stands in for cardiovascular events — ENHANCE lowered LDL a further 16.5% and the wall thickness did not improve
Where it acts
Hepatocyte cytoplasm — the endoplasmic reticulum membrane of the liver cell, where HMG-CoA reductase sits, reached through the OATP1B1 transporter
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · AGG2FN16EV · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 158 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Cholesterol
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
△Only a number moved16 registered test measure.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Fertility and sexual health
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
△Only a number moved1 registered test measure.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Cholesterol
ldl c from baseline to week 12; low density lipoprotein cholesterol; ldl c from the start of the study; fasting plasma low density lipoprotein cholesterol; ldl c/hdl c; triglycerides from baseline to final visit; ldl c; low density lipoprotein cholesterol at 12 weeks
Fertility and sexual health
serum testosterone
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
△ Only a number moved
16 registered test measure.
— Not recorded
Harms were not a registered measure for this goal.
… Waiting for a reviewer
Who was studied is listed further down the page.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
All-cause mortality in patients with angina or previous myocardial infarction and serum cholesterol 5.5 to 8.0 mmol/L
✓ The study showed what it set out to show
Who was studied
4S — Scandinavian Simvastatin Survival Study (Lancet 1994;344:1383-1389)
182 deaths (8%) against 256 (12%); relative risk 0.70 (95% CI 0.58 to 0.85), p=0.0003 over a median 5.4 years
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Non-cardiovascular deaths were 46 against 49 — the reduction in coronary death was not offset by a rise elsewhere, which was the specific fear the trial was designed to answer. Enrolment required cholesterol between 5.5 and 8.0 mmol/L, so the result does not by itself extend to people outside that range; HPS was the trial that tested that.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, taken once daily in the evening; also an oral suspension (Flolipid)
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
All-cause mortality 12.9% against 14.7%, p=0.0003; major vascular events 19.8% against 25.2%, a 24% proportional reduction (95% CI 19 to 28), p<0.0001
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The reduction in major vascular events was not significant during the first year and became highly significant in every subsequent year, so a short trial of the same drug would have reported a null result. Average compliance was 85% and 17% of the placebo group took a non-study statin, so the intention-to-treat comparison understates the effect of actually taking the drug.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, taken once daily in the evening; also an oral suspension (Flolipid)
Interval reported. 95% CI 19 to 28), p<0
Written into the record, not signed off as a reviewed claim.
24.5% against 25.7%; risk ratio 0.94 (95% CI 0.88 to 1.01), p=0.10 over a mean 6.7 years, for an average 0.35 mmol/L greater LDL reduction
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Myopathy in 53 (0.9%) on 80 mg against two (0.03%) on 20 mg. The FDA subsequently restricted the 80 mg dose to patients already tolerating it for twelve months or more, and the brand stopped marketing that strength.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, taken once daily in the evening; also an oral suspension (Flolipid)
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Change in mean carotid-artery intima-media thickness over 24 months, simvastatin 80 mg plus ezetimibe against simvastatin 80 mg alone, in familial hypercholesterolaemia
✗ The study did not show it
Who was studied
ENHANCE (N Engl J Med 2008;358:1431-1443; NCT00552097)
Change in carotid IMT 0.0111 ± 0.0038 mm on the combination against 0.0058 ± 0.0037 mm on simvastatin alone, p=0.29, despite a 16.5% lower end-of-study LDL (p<0.01)
Repeated elsewhere
Partially Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Side-effect and safety profiles were similar between arms. The trial is on this page for what it says about surrogate endpoints rather than about ezetimibe: IMPROVE-IT later found a real if modest event reduction for the same combination in 18,144 patients (32.7% against 34.7% at seven years, HR 0.936, p=0.016).
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, taken once daily in the evening; also an oral suspension (Flolipid)
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
■Living longer, or avoiding a major eventEvidence recorded. Death, a heart attack, a stroke, a hospital stay.2 registered measures of this kind. 1 written-up study measured this and did not show a benefit.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
□Symptoms and quality of lifeNo evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.21 registered measures of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Drosophila (fruit fly), Mouse, Rat. A result in animals says what to test next. It does not say what happens in people.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Where a source records it acting
Liver: Sustained inhibition of cholesterol synthesis in the liver
US prescribing information · 00896fff-081d-4553-be8c-1999a8a73dda · read 2026-08-27
Blood and vessels: Uptake of LDL-C from blood to the liver, decreasing plasma LDL-C and total cholesterol
US prescribing information · 00896fff-081d-4553-be8c-1999a8a73dda · read 2026-08-27
Start
Simvastatin
What a person takes: Oral tablet, taken once daily in the evening; also an oral suspension (Flolipid).
The measurement behind this step
Absorbed and then heavily extracted by the liver on first pass, so under 5% of the parent reaches the general circulation. Plasma concentrations of total radioactivity peak at four hours and fall to about 10% of peak by twelve hours. Peak concentrations of active and total inhibitors are attained within 1.3 to 2.4 hours. A low-fat meal does not affect the plasma profile. Metabolised by CYP3A4 to simvastatin acid and its 6′-hydroxy, 6′-hydroxymethyl and 6′-exomethylene derivatives; 13% of a dose is excreted in urine and 60% in faeces. Evening dosing exploits the fact that hepatic cholesterol synthesis runs highest overnight.
Getting in
What you swallow is not the drug
The tablet contains a closed-ring molecule that inhibits almost nothing. The body has to snap the ring open first, and the opened form is what does the work.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Simvastatin is a lactone prodrug hydrolysed in vivo to simvastatin acid, the β-hydroxyacid. The label states that the acid and its metabolites are the inhibitors of HMG-CoA reductase. Both parent and acid are about 95% plasma-protein bound.
On the first pass through the liver, most of the dose is captured before it ever reaches the rest of the body. That is deliberate: the liver is where it needs to be.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Extensive first-pass hepatic extraction leaves systemic availability of the parent below 5%. Uptake into the hepatocyte is carrier-mediated through OATP1B1, the product of SLCO1B1. Peak concentrations of active and total inhibitors are attained within 1.3 to 2.4 hours.
Cholesterol is built in the liver along a long assembly line. Simvastatin acid jams the slowest station on that line, so the whole line backs up.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Simvastatin acid inhibits HMG-CoA reductase, the rate-limiting enzyme converting HMG-CoA to mevalonate, the committed precursor of cholesterol. The acid is a transition-state analogue of the substrate, which is why the open ring is required and the lactone is inert.
The liver responds by pulling cholesterol out of the blood
Short of cholesterol it can no longer make, the liver cell puts more hooks on its surface to grab cholesterol-carrying particles out of the bloodstream. That, not the blocked enzyme, is what lowers your blood level.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The label states that inhibition of HMG-CoA reductase accelerates expression of LDL receptors, followed by uptake of LDL-C from blood into the liver, decreasing plasma LDL-C and total cholesterol; sustained inhibition also decreases VLDL. Maximum LDL-C reduction is usually reached by four weeks and maintained thereafter.
In people who already have heart disease, that chain of events translates into measurably fewer deaths — the finding that made statins standard treatment.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
4S: all-cause death 8% against 12% over a median 5.4 years in 4,444 patients, RR 0.70 (95% CI 0.58 to 0.85, p=0.0003). HPS: all-cause death 12.9% against 14.7% in 20,536 high-risk adults, p=0.0003, with major vascular events down 24% (19.8% against 25.2%, p<0.0001).
The same route that carries it in decides who gets hurt
If the transporter that carries the drug into the liver works poorly, more of the active form stays in the bloodstream, and that is where the muscle injury comes from.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
SLCO1B1 rs4149056 reduces OATP1B1-mediated hepatic uptake. Odds ratio for myopathy 4.5 (95% CI 2.6 to 7.7) per C allele copy, 16.9 (95% CI 4.7 to 61.1) for CC against TT; more than 60% of myopathy cases in the 80 mg population were attributable to the variant. Dose-stratified myopathy on the label: 0.03% at 20 mg, 0.08% at 40 mg, 0.61% at 80 mg.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
No registered study measured anything of this kind.
Measured
Things only a test, a scale or a device shows.
ldl c from baseline to week 12
plaque inflammation
low density lipoprotein cholesterol
ldl c from the start of the study
fasting plasma low density lipoprotein cholesterol
ldl c/hdl c
triglycerides from baseline to final visit
ldl c
low density lipoprotein cholesterol at 12 weeks
ldl receptor mrna expression
and 11 more.
Meaningful
Things that change how a life goes, not only a number.
any stroke at 90 days
stroke severity
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (17)
low density lipoproteins after 6 weeks
csf abeta levels
intima media thickness of carotid artery
overall response rate
hmg coa reductase activity
hmg coa reductase mrna expression
panel of biomarkers from baseline
auc0 t total ezetimibe
auc0 t rosuvastatin
auc0 t fenofibric acid
auc0 t atorvastatin acid
auc0 t nicotinic acid
auc0 t nicotinuric acid
distance walked in six minutes
reduction in oxldl levels
hscrp
modify lipids
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Adults with established coronary, cerebrovascular or peripheral arterial disease, adults with diabetes at high coronary risk, and adults and children from age ten with familial hypercholesterolaemia.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
Who a named study recorded including and excluding
label:clinical-studies recorded its participants as: 4,444 adult patients; approximately 18% of the study population was female; median duration 5.4 years.
US prescribing information · 00896fff-081d-4553-be8c-1999a8a73dda · read 2026-08-27
It included: adult patients with CHD (history of angina and/or a previous myocardial infarction); baseline total cholesterol (total-C) between 212 and 309 mg/dL; on a lipid-lowering diet.
US prescribing information · 00896fff-081d-4553-be8c-1999a8a73dda · read 2026-08-27
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness of simvastatin in patients 10 to 17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial in adolescent boys and in girls who were at least 1 year post-menarche.”
US prescribing information · 37860f3f-984e-419a-a262-3bacc766953e · read 2026-08-30
On older people, the label states: “Of the 2,423 patients who received simvastatin in Phase III clinical studies and the 10,269 patients in the Heart Protection Study who received simvastatin, 363 (15%) and 5,366 (52%), respectively were ≥65 years old.”
US prescribing information · 37860f3f-984e-419a-a262-3bacc766953e · read 2026-08-30
On people who are pregnant, the label states: “Category X [See Contraindications (4). ] Simvastatin is contraindicated in women who are or may become pregnant.”
US prescribing information · 37860f3f-984e-419a-a262-3bacc766953e · read 2026-08-30
On people who are breastfeeding, the label states: “It is not known whether simvastatin is excreted in human milk.”
US prescribing information · 37860f3f-984e-419a-a262-3bacc766953e · read 2026-08-30
On people with reduced liver function, the label states: “Simvastatin is contraindicated in patients with active liver disease which may include unexplained persistent elevations in hepatic transaminase levels [see Contraindications (4) and Warnings and Precautions (5.3)].”
US prescribing information · 37860f3f-984e-419a-a262-3bacc766953e · read 2026-08-30
On people with reduced kidney function, the label states: “Caution should be exercised when simvastatin is administered to patients with severe renal impairment. [See Dosage and Administration (2.6). ]”
US prescribing information · 37860f3f-984e-419a-a262-3bacc766953e · read 2026-08-30
Where the result stopped carrying
SEARCH: quadrupling the dose did not significantly reduce major vascular events (p=0.10)
ENHANCE: the imaging surrogate did not move despite a large additional LDL reduction
The 80 mg dose was approved, marketed, and then restricted by the FDA to patients who had already tolerated it for twelve months; the brand no longer markets that strength at all
Before 4S, cholesterol-lowering trials had repeatedly reduced coronary events without reducing total mortality, which is exactly why 4S was designed around all-cause death
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablet, taken once daily in the evening; also an oral suspension (Flolipid)
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S3.
No source is stored against this line.
What is in the pack
Absorbed and then heavily extracted by the liver on first pass, so under 5% of the parent reaches the general circulation. Plasma concentrations of total radioactivity peak at four hours and fall to about 10% of peak by twelve hours. 4 hours. A low-fat meal does not affect the plasma profile. Metabolised by CYP3A4 to simvastatin acid and its 6′-hydroxy, 6′-hydroxymethyl and 6′-exomethylene derivatives; 13% of a dose is excreted in urine and 60% in faeces. Evening dosing exploits the fact that hepatic cholesterol synthesis runs highest overnight.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Contraindicated with strong CYP3A4 inhibitors (selected azole antifungals, macrolide antibiotics, antivirals and nefazodone), with ciclosporin, danazol or gemfibrozil, in acute liver failure or decompensated cirrhosis, and in hypersensitivity — anaphylaxis, angioedema and Stevens-Johnson syndrome have been reported. Myopathy and rhabdomyolysis are the defining risks: incidence rises with dose, with age 65 and over, with uncontrolled hypothyroidism, with renal impairment and with interacting drugs, and the label records that Chinese patients may be at higher risk. Rare immune-mediated necrotising myopathy has been reported and does not resolve simply on stopping. Transaminase rises occur, occasionally persistent, with rare reports of fatal and non-fatal hepatic failure. Increases in HbA1c and fasting glucose have been reported with statins including this one.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
These are reports people sent to a regulator. They do not show the medicine caused the reaction.
Nobody counted how many people took the medicine and reported nothing.
The same event can be reported more than once, and many reports are incomplete.
News coverage, lawsuits and new warnings change how often people report.
A count is not a rate and not a risk.
Simvastatin appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 27617 reaction mentions were counted. One report can name several reactions.
liver function test abnormal — 990 reaction mentions
myositis — 734 reaction mentions
immune-mediated myositis — 474 reaction mentions
open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet, taken once daily in the evening; also an oral suspension (Flolipid)
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Plasma concentrations of total radioactivity peak at four hours and fall to about 10% of peak by twelve hours. 4 hours. A low-fat meal does not affect the plasma profile. Metabolised by CYP3A4 to simvastatin acid and its 6′-hydroxy, 6′-hydroxymethyl and 6′-exomethylene derivatives; 13% of a dose is excreted in urine and 60% in faeces. Evening dosing exploits the fact that hepatic cholesterol synthesis runs highest overnight.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
218 products list this as an active ingredient in the United States drug directory. 178 of them contain it and nothing else.
FDA National Drug Code directory · 72189-427 · read 2026-08-29
They are sold as powder, tablet and tablet, film coated, taken oral.
FDA National Drug Code directory · 72189-427 · read 2026-08-29
The regulator's established pharmacologic class for it is hmg-coa reductase inhibitor [epc] and hydroxymethylglutaryl-coa reductase inhibitors [moa].
FDA National Drug Code directory · 72189-427 · read 2026-08-29
121 published labels name it as an active ingredient. 111 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 37860f3f-984e-419a-a262-3bacc766953e · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 37860f3f-984e-419a-a262-3bacc766953e · read 2026-08-29
SIMVASTATIN is tablets at Tablets: 5 mg, 10 mg; 20 mg; 40 mg; 80 mg, recorded as prescription product; fda label in effect 2026-02-26 in the United States.
US prescribing information · 00896fff-081d-4553-be8c-1999a8a73dda · read 2026-08-27
Recorded price in US: 0.02792–0.09876 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 99 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Simvastatin studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That carotid intima-media thickness stands in for cardiovascular events — ENHANCE lowered LDL a further 16.5% and the wall thickness did not improve
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That more LDL lowering is always better regardless of the molecule delivering it: at 80 mg this molecule bought 6% fewer events, not significantly, at thirty times the myopathy rate
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That red yeast rice is a gentler alternative, when its active constituent is chemically identical to a prescription statin at an unregulated and highly variable dose
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the glycaemic signal in the current label is quantified as precisely as the mortality benefit, when it was never a prespecified endpoint in either mortality trial
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Simvastatin are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
4S: the first trial in which cholesterol lowering reduced total mortality
In plain words
Four and a half thousand people with heart disease took simvastatin or placebo for five and a half years. Twelve per cent of the placebo group died against eight per cent on the drug. That gap is the reason statins are prescribed.
What was measured
All-cause mortality over a median 5.4 years in 4,444 patients with coronary heart disease
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
4S randomised 4,444 patients with angina or previous myocardial infarction and serum cholesterol 5.5 to 8.0 mmol/L on a lipid-lowering diet to double-blind simvastatin or placebo. Over a median 5.4 years, simvastatin produced mean changes of −25% in total cholesterol, −35% in LDL cholesterol and +8% in HDL. 256 patients (12%) in the placebo group died against 182 (8%) on simvastatin: relative risk of death 0.70 (95% CI 0.58 to 0.85, p=0.0003). Coronary deaths were 189 against 111 (RR 0.58, 95% CI 0.46 to 0.73), while non-cardiovascular deaths were 49 and 46 — the trial did not trade cardiac deaths for other ones, which is precisely what the earlier cholesterol-lowering literature had been accused of. Major coronary events occurred in 622 (28%) against 431 (19%), RR 0.66 (95% CI 0.59 to 0.75, p<0.00001).
Written into the record, not signed off as a reviewed claim
The Heart Protection Study moved the target from a number to a risk
In plain words
Twenty thousand high-risk people were given simvastatin or placebo regardless of their cholesterol. The benefit was the same in people whose cholesterol was already low as in people whose cholesterol was high. Treatment stopped being about the number on the test.
What was measured
Major vascular events and all-cause mortality in 20,536 high-risk adults, stratified by baseline LDL cholesterol
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
HPS randomised 20,536 UK adults aged 40 to 80 with coronary disease, other occlusive arterial disease or diabetes to 40 mg simvastatin daily or placebo for five years. All-cause mortality was 1,328 (12.9%) against 1,507 (14.7%), p=0.0003, driven by an 18% proportional reduction in coronary death (5.7% against 6.9%, p=0.0005). Major vascular events fell 24% (95% CI 19 to 28): 2,033 (19.8%) against 2,585 (25.2%), p<0.0001. The proportional reduction was similar and significant in every subgroup, including — the authors flagged this as most notable — participants presenting with LDL cholesterol below 3.0 mmol/L (116 mg/dL) or total cholesterol below 5.0 mmol/L. The conclusion the field drew, and now acts on, is that the size of the benefit depends chiefly on overall vascular risk rather than on blood lipid concentration. The annual excess risk of myopathy on this regimen was about 0.01%.
Written into the record, not signed off as a reviewed claim
SEARCH: four times the dose, thirty times the myopathy, no significant extra benefit
In plain words
Twelve thousand heart attack survivors were randomised to 80 mg or 20 mg of the same drug. The higher dose lowered cholesterol a little further and did not significantly reduce events. It caused muscle injury in about one in a hundred people against one in five thousand.
What was measured
Major vascular events and myopathy incidence, 80 mg against 20 mg simvastatin, mean 6.7 years
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
SEARCH randomised 12,064 men and women aged 18 to 80 with a history of myocardial infarction to 80 mg or 20 mg simvastatin daily. Over a mean 6.7 years, 80 mg produced an average 0.35 mmol/L greater LDL reduction. Major vascular events occurred in 1,477 (24.5%) on 80 mg against 1,553 (25.7%) on 20 mg — a 6% proportional reduction, risk ratio 0.94 (95% CI 0.88 to 1.01), p=0.10. Vascular deaths were 565 (9.4%) against 572 (9.5%). Against two (0.03%) cases of myopathy on 20 mg there were 53 (0.9%) on 80 mg. The authors were careful about what this does and does not show: a 6% event reduction for 0.35 mmol/L is consistent with the rest of the statin literature, so the trial is not evidence that further LDL lowering fails — it is evidence that this molecule is the wrong vehicle for it, and the interpretation says so, that intensive LDL lowering can be achieved safely with other regimens.
Written into the record, not signed off as a reviewed claim
The regulator restricted a dose it had approved
In plain words
The 80 mg tablet was approved, marketed and widely prescribed. In 2011 the FDA said it should not be started in anyone new, and the brand no longer makes it at all.
What was measured
Dose-stratified myopathy and rhabdomyolysis incidence, and the resulting change to the licensed maximum dose
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The current ZOCOR label states that an 80 mg daily dosage is restricted to patients who have been taking simvastatin 80 mg daily chronically, for twelve months or more, without evidence of muscle toxicity, and that the maximum recommended dosage is 40 mg once daily. It records that in 24,747 treated patients followed a median four years, myopathy incidence was approximately 0.03% at 20 mg, 0.08% at 40 mg and 0.61% at 80 mg, and that in the 12,064-patient SEARCH population it was 0.02% at 20 mg and 0.9% at 80 mg, with rhabdomyolysis at approximately 0% and 0.4%. The label further directs that patients who need a high-intensity statin be prescribed a different LDL-lowering treatment rather than a higher simvastatin dose, and states that the brand is no longer marketed in the 5 mg and 80 mg strengths. A dose that a regulator approves and then withdraws from new starts is the clearest kind of evidence audit there is: the harm was dose-dependent, it was measurable, and it took a 12,000-patient trial to make it visible against a background rate of one in five thousand.
Source
ZOCOR (simvastatin) United States prescribing information, sections 2.1 and 5.1 (NDA 019766)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
One common gene variant explains most of the muscle injury
In plain words
A genome-wide search across people who developed muscle injury on high-dose simvastatin found a single culprit: a variant in the gene for the transporter that carries the drug into the liver. Fifteen per cent of people carry it, and it accounts for more than sixty per cent of the cases.
What was measured
Odds ratio for myopathy per copy of the SLCO1B1 rs4149056 C allele in a genome-wide association study
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The SEARCH Collaborative Group scanned about 300,000 markers in 85 subjects with definite or incipient myopathy against 90 controls, all taking 80 mg simvastatin daily within the 12,000-patient trial. A single strong association emerged at rs4363657 in SLCO1B1 on chromosome 12 (p=4×10⁻⁹), in near-complete linkage disequilibrium (r²=0.97) with the nonsynonymous rs4149056. SLCO1B1 encodes OATP1B1, which carries statins into the hepatocyte. The C allele prevalence was 15%; the odds ratio for myopathy was 4.5 (95% CI 2.6 to 7.7) per copy and 16.9 (95% CI 4.7 to 61.1) for CC against TT homozygotes. More than 60% of myopathy cases in this population were attributable to the C variant, and the association replicated in a 20,000-participant trial of 40 mg simvastatin. The mechanism is coherent with everything else on this page: less hepatic uptake means more simvastatin acid left in the circulation, and the muscle is where it does damage.
Written into the record, not signed off as a reviewed claim
ENHANCE: more LDL lowering, no movement in the artery wall
In plain words
Adding a second cholesterol drug to high-dose simvastatin lowered LDL by a further sixteen per cent. The thickness of the artery wall, which the trial was designed to measure, did not improve at all — if anything it went the other way.
What was measured
That a surrogate imaging endpoint — carotid intima-media thickness — tracks cardiovascular events closely enough to substitute for them
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
ENHANCE randomised 720 patients with familial hypercholesterolaemia to 80 mg simvastatin plus either placebo or 10 mg ezetimibe for 24 months, with carotid intima-media thickness by B-mode ultrasound as the primary outcome. Mean change in carotid IMT was 0.0058 ± 0.0037 mm on simvastatin alone against 0.0111 ± 0.0038 mm on the combination (p=0.29) — numerically worse on the arm with lower cholesterol. End-of-study LDL was 192.7 mg/dL against 141.3 mg/dL, a 16.5% between-group difference, p<0.01, with greater reductions in triglycerides and C-reactive protein too. Every lipid measurement moved in the expected direction and the imaging surrogate did not follow. The honest reading is not that ezetimibe fails — IMPROVE-IT later randomised 18,144 post-acute-coronary-syndrome patients to simvastatin 40 mg with or without ezetimibe and found a primary event rate of 32.7% against 34.7% at seven years (HR 0.936, 95% CI 0.89 to 0.99, p=0.016). The honest reading is that carotid intima-media thickness was not a reliable stand-in for events, and the field discovered that by being wrong in public.
Written into the record, not signed off as a reviewed claim
The label now warns about blood sugar, which the mortality trials did not measure
In plain words
Statins raise blood sugar slightly. The label says so. None of the big survival trials were designed to measure that, and it was added to the class label years after they finished.
What was measured
That the size of the glycaemic effect is known with the same confidence as the mortality effect, when one was a prespecified randomised endpoint and the other was not measured in the trials at all
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The ZOCOR warnings section states that increases in HbA1c and fasting serum glucose have been reported with statins including simvastatin. This entry arrived through a class-wide labelling change long after 4S and HPS reported, and neither of those trials was powered or designed to detect it. What follows from that is a genuine asymmetry that a reader should hold in mind: the mortality benefit was measured prospectively in randomised trials with tens of thousands of participants, and the glycaemic signal was assembled afterwards from meta-analysis and surveillance. They are not equally strong measurements, and the direction of that inequality favours the benefit.
Source
ZOCOR (simvastatin) United States prescribing information, section 5, Increases in HbA1c and Fasting Serum Glucose Levels (NDA 019766)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
How many documents were read
111 documents were read for this substance.
RNAWiki source record
111 of them state the same tMax, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
AGG2FN16EV
CAS registry number
79902-63-9
PubChem compound
54454
RxNorm concept
36567
Checks this page had to pass
✓ Passed
Identity resolved
no open identity hold
✓ Passed
No unresolved merge across substance families
no quarantine open
✓ Passed
Every public sentence names a source
The opening statement carries the origin: Written into the record, not signed off.
✗ Not passed
Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
✓ Passed
No internal keys in reader text
enforced by the copy-contract test over the rendered page
✓ Passed
Safety mode resolved
Suppression classes recorded: S3.
✓ Passed
Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
31 approved applications cover products containing this substance. The earliest was NDA019766, approved 19911223 to ORGANON.
This order is fixed in code and does not count clicks or time on the page.
What is not here
4 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
The statin that ended the argument about whether lowering cholesterol saves lives — 4S cut all-cause death from 12% to 8% in 4,444 people with coronary disease (RR 0.70, 95% CI 0.58 to 0.85, p=0.0003) — and the same molecule at 80 mg caused myopathy in 0.9% against 0.03% at 20 mg while failing to significantly reduce vascular events, which is why the FDA restricted the highest dose it had itself approved.
Recorded evidence blocks (14)
Q2
What did Simvastatin's largest trial (2133900 people) and its longest (14 years) measure?
2133900 people in Simvastatin's largest registered study, 14 years in its longest registered window, measuring The Primary efficacy measure is hospital mortality to day 28. ClinicalTrials.gov · 2026-09-01
100 phase3, 97 phase4, 93 phase2, 88 phase1, 56 na, 13 early phase1, 8 na or unstated; NCT01653223; 2026-12. Last human test completed 2026, NCT07692620.
Interpretation These counts include studies where Simvastatin was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase3
100
phase4
97
phase2
93
phase1
88
na
56
early phase1
13
2 more recorded rows
na or unstated
8
Last recorded human testNCT07692620
2026-05-30
recorded 2026-09-01 · last checked 2026-09-04
Q3
From Drosophila to human: where has Simvastatin shown lifespan?
622 mice; cohorts C2006; cohort rows are the workbook's own printed values; no median, percent change or survival statistic is derived from the per-animal data
Show the evidence
ITP cohort
C2006
simvastatin; 120; 10.0 months; f, m; ITP_C2006_Lifespan.xlsx
C2006
simvastatin; 12; 10.0 months; f, m; ITP_C2006_Lifespan.xlsx
"AIM-HIGH was stopped on the recommendation of the DSMB because of lack of efficacy of niacin in preventing primary outcome events."; 45 of 429 registered studies
Show the evidence
Trial
NCT00120289
terminated; "AIM-HIGH was stopped on the recommendation of the DSMB because of lack of efficacy of niacin in preventing primary outcome events."
NCT00208117
terminated; "Unable to enroll subjects"
NCT00249899
terminated; "Overall profile of the compound does not offer significant clinical advantage to patients over currently available lipid lowering agents"
NCT00306826
withdrawn; "financial support withdrawn"
NCT00487461
terminated; "Study PI left the institution and study was stopped at that time."
NCT00503763
withdrawn; "We found out that there is another study on the same issue"
14 further recorded trials
NCT00528580
terminated; "Inadequate recruitment"
NCT00532311
terminated; "Overall profile of the compound does not offer significant clinical advantage to patients over currently available lipid lowering agents"
NCT00575965
terminated; "Slow accrual led to early study termination."
NCT00588471
terminated; "The study was terminated because not enough subjects could be recruited."
NCT00605995
terminated; "Enrollment was slower than anticipated by the investigators and the funding research foundation."
NCT00651391
terminated; "Slow enrollment"
NCT00672464
withdrawn; "lack of funding"
NCT00718328
terminated; "Poor recruitment, trial terminated"
NCT00738972
terminated; "Study terminated early due to sample size, not possible to perform further statistical analysis."
NCT00743197
terminated; "Terminated due to departure of PI from institution."
NCT00746603
terminated; "Poor enrollment"
NCT00946166
withdrawn; "Investigator left institution."
NCT00990834
withdrawn; "Unable to recruit subjects."
NCT01057758
terminated; "stopped for futility"
recorded 2026-09-01 · last checked 2026-09-04
Q6
Mouse studies of Simvastatin used 12 (lo) and 120 (hi) ppm — over how long?
studies of Simvastatin used the recorded amount. clinicaltrials.gov+jax-mpd-itp · 2026-09-04
22 recorded entries; mouse, human; also "12 (lo) and 120 (hi) ppm", "Simvastatin (20mg versus 80mg/day)", "Simvastatin 20 mg"
Show the evidence
mouse
simvastatin C2006
12 (lo) and 120 (hi) ppm
simvastatin C2006
12 (lo) and 120 (hi) ppm
human
NCT00125060
Simvastatin (20mg versus 80mg/day)
NCT00125593
Simvastatin 20 mg
NCT00202878
Placebo for simvastatin 40 mg
NCT00202878
Placebo for ezetimibe 10 mg/simvastatin 40 mg combination
NCT00330980
20 mg Simvastatin
NCT00404599
simvastatin 40mg
12 more recorded rows
humanNCT00423579
Ezetimibe/Simvastatin 10/20 mg
humanNCT00423579
simvastatin 40 mg
humanNCT00474123
Simvastatin 80 mg/day for 6 weeks
humanNCT00474123
Simvastatin 80 mg (Zocor)
humanNCT00474123
Ezetimibe 10 mg / Simvastatin 20 mg
humanNCT00481351
Simvastatin 20mg plus ezetimibe 10mg
humanNCT00481351
simvastatin 20mg
humanNCT00481351
Simvastatin 80mg
humanNCT00487461
Simvastatin 40 mg
humanNCT00487461
Simvastatin 80 mg
humanNCT00560170
10mg/10mg of Ezetimibe/Simvastatin (Vytorin)
humanNCT00704548
Simvastatin 40mg
recorded 2026-09-04 · last checked 2026-09-04
Q7
Which of any stroke at 90 days, attaining ncep ldl c target at week 16 and attaining ncep ldl c target at week 44 did Simvastatin's trials measure?
any stroke at 90 days, attaining ncep ldl c target at week 16 and attaining ncep ldl c target at week 44 lead 40 outcome terms across Simvastatin's trials. ClinicalTrials.gov · 2026-09-01
plaque inflammation, low density lipoprotein cholesterol, ldl c from the start of the study, fasting plasma low density lipoprotein cholesterol, low density lipoproteins after 6 weeks and ldl c/hdl c follow.
Show the evidence
ldl c from baseline to week 12
1
any stroke at 90 days
1
stroke severity
1
plaque inflammation
1
low density lipoprotein cholesterol
1
ldl c from the start of the study
1
14 more recorded rows
fasting plasma low density lipoprotein cholesterol
1
low density lipoproteins after 6 weeks
1
ldl c/hdl c
1
triglycerides from baseline to final visit
1
csf abeta levels
1
intima media thickness of carotid artery
1
ldl c
1
low density lipoprotein cholesterol at 12 weeks
1
overall response rate
1
hmg coa reductase activity
1
hmg coa reductase mrna expression
1
ldl receptor mrna expression
1
ldl receptor protein
1
panel of biomarkers from baseline
1
recorded 2026-09-01 · last checked 2026-09-04
Q8
Which of Simvastatin's 25 ongoing trials reports first?
"Myocardial Protection Effect of Simvastatin Undergoing Cardiac Surgery"; n 369; "troponin"; 2026-12
NCT02735707
"Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia"; n 20000; "All-cause mortality"; 2028-02
NCT02968810
"Simvastatin in Preventing Liver Cancer in Patients With Liver Cirrhosis"; n 52; "Change in Serum AFP-L3%"; 2027-12-23
NCT03131726
"Treatment of Graves´ophthalmopathy with Simvastatin (GO-S)"; n 80; "Change in Clinical activity score (CAS) after 6 months"; 2028-03-30
NCT03324425
"Simvastatin Plus Dual Anti-HER2 Therapy for Metastatic Breast Cancer"; n 5; "Objective Response"; 2030-12
NCT03400826
"Effects of Simvastatin on Uterine Leiomyoma Size"; n 60; "Change in Tumor size volume pre and post study intervention"; 2026-07-31
14 further recorded trials
NCT03654053
"Multi-Center Study of the Effects of Simvastatin on Hepatic Decompensation and Death in Subjects Presenting With High-Risk Compensated Cirrhosis"; n 142; "Survival free from hepatic decompensation"; 2026-12-31
NCT03889795
"Phase IB Metformin, Digoxin, Simvastatin in Solid Tumors"; n 15; "Maximum Tolerated Dose and/or Recommended Dose within the tested C3 dose range"; 2027-12-30
NCT04133792
"Effect of Simvastatin on the Prognosis of Primary Primary Sclerosing Cholangitis (PSC)"; n 571; "Overall survival"; 2030-03-31
NCT04514029
"Neurotoxicity Prophylaxis With Intrathecal Dexamethasone and Simvastatin Post Axi-Cel"; n 37; "Number of patients completing two-thirds of their assigned treatment"; 2026-12
NCT04971577
"Efficacy of Simvastatin in Alcoholic Liver Fibrosis"; n 90; "Change from baseline biopsy in histological fibrosis Ishak score (0-4 range. higher scores mean a worse result)"; 2027-12
NCT05059626
"Endometriosis and Microvascular Dysfunction; Simvastatin and Duavee"; n 28; "Change in skin blood flow"; 2026-12-31
NCT05464810
"Letrozole With and Without Simvastatin for the Treatment of Stage I-III Hormone Receptor Positive, HER2 Negative Breast Cancer"; n 40; "Mean percentage change in Ki-67"; 2028-04-15
NCT05550415
"The Role of Simvastatin in the Epithelial-Mesenchymal Transition Process of Breast Cancer"; n 26; "Vimentin Expression"; 2025-08
NCT05586360
"T-reg Function Changes: a Novel Immune Regulatory Effect Underlying Benefit of Statin Use on Lethal Prostate Cancer"; n 36; "Intra-prostatic YAP-mediated T-reg dysfunction in total tissue area"; 2027-08-01
NCT05771675
"Simvastatin Treatment to Improve Patient-reported Outcomes in Patients With Chronic Pancreatitis"; n 90; "Examine the feasibility and acceptability of testing the effect of simvastatin on health-related quality of life outcomes in patients with recurrent acute and chronic pancreatitis."; 2028-06
NCT05821556
"Valproic Acid/Simvastatin Plus Gemcitabine/Nab-paclitaxel Based Regimens in Untreated Metastatic Pancreatic Adenocarcinoma Patients"; n 240; "Progression Free Survival (PFS)"; 2027-06
NCT06399783
"Topical Simvastatin Versus Topical Steroid in Treatment of Alopecia Areata"; n 54; "Evaluation of hair regrowth in alopecia areata using SALT score."; 2027-12-01
NCT06431919
"Carvedilol + Simvastatin vs. Carvedilol Alone for Cirrhosis and Cirrhotic Cardiomyopathy and Impact on Hepatic Decompensation and Survival"; n 260; "Time to acute decompensation event"; 2028-02
NCT06858332
"Lipoprotein(a) Levels in Patients With Atherosclerotic Cardiovascular Diseases in Russia"; n 2382; "Percentage of patients (%) with Lp(a) ≥125 nmol/L"; 2027-09-30
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which running trial of Simvastatin could settle lifespan?
NCT03654053 measures Survival free from hepatic decompensation, reading out 2026-12-31.
4 open trials; n 142; "Multi-Center Study of the Effects of Simvastatin on Hepatic Decompensation and Death in Subjects Presenting With High-Risk Compensated Cirrhosis"
Show the evidence
Trial
NCT03654053
"Multi-Center Study of the Effects of Simvastatin on Hepatic Decompensation and Death in Subjects Presenting With High-Risk Compensated Cirrhosis"; n 142; "Survival free from hepatic decompensation"; 2026-12-31
NCT05821556
"Valproic Acid/Simvastatin Plus Gemcitabine/Nab-paclitaxel Based Regimens in Untreated Metastatic Pancreatic Adenocarcinoma Patients"; n 240; "Progression Free Survival (PFS)"; 2027-06
NCT02735707
"Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia"; n 20000; "All-cause mortality"; 2028-02
NCT04133792
"Effect of Simvastatin on the Prognosis of Primary Primary Sclerosing Cholangitis (PSC)"; n 571; "Overall survival"; 2030-03-31
Q10
Which 188 trials of Simvastatin posted no result?
Posted no result
188 of 188 completed trials
Registrations
NCT00004266, NCT00905541, NCT02587390, NCT00000553, NCT03884452 and NCT00000941, and 182 more
Completion dates
oldest 1999-07; newest 2024-08-25
Show the evidence
Trial
NCT00004266
1999-07
NCT00905541
2000-03
NCT02587390
2000-07
NCT00000553
2001-02
NCT03884452
2001-05-24
NCT00000941
2002-03
14 further recorded trials
NCT03885921
2003-07-08
NCT00330980
2004-03
NCT00125060
2004-04
NCT00652301
2004-04
NCT00654446
2004-04
NCT00317993
2004-07
NCT00652444
2004-08
NCT00653835
2004-08-01
NCT00654173
2004-09
NCT00654407
2004-09
NCT00650663
2004-09-01
NCT00654537
2004-10
NCT00365638
2005-02
NCT00650819
2005-02-01
Q11
At the median, Simvastatin's trials enrolled 52.5 people — anything larger?
Median enrolment
52.5
Largest enrolment
2133900
Registered trials counted
422
Q12
What do 27617 spontaneous reports say about Simvastatin — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Simvastatin appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 27617 reaction mentions were counted: myalgia 7000; rhabdomyolysis 6545; drug interaction 3626; blood creatine phosphokinase increased 3162. open-targets-adr · CHEMBL1064 · 2026-06-24
Show the evidence
myalgia
7000
rhabdomyolysis
6545
drug interaction
3626
blood creatine phosphokinase increased
3162
muscular weakness
2046
myopathy
1546
4 more recorded rows
renal failure acute
1494
liver function test abnormal
990
myositis
734
immune-mediated myositis
474
recorded 2026-06-24 · last checked 2026-09-04
Q13
Simvastatin and CYP3A4 and OATP1B1: shared by which compounds?
CYP3A4 and OATP1B1 appear in Simvastatin's recorded interaction sentences, 4 in all. openfda-label+europepmc · 2026-08-30
Interpretation pharmacokinetics
Show the evidence
CYP3A4
pharmacokinetics
Inhibitors of CYP3A4 can raise the plasma levels of HMG-CoA reductase inhibitory activity and increase the risk of myopathy [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ].
pharmacokinetics
For example, cyclosporine has been shown to increase the AUC of statins; although the mechanism is not fully understood, the increase in AUC for simvastatin acid is presumably due, in part, to inhibition of CYP3A4 and/or OATP1B1.
pharmacokinetics
This indicates that simvastatin is not an inhibitor of CYP3A4, and, therefore, is not expected to affect the plasma levels of other drugs metabolized by CYP3A4.
pharmacokinetics
TABLE 3:Effect of Coadministered Drugs or Grapefruit Juice on Simvastatin Systemic Exposure In a study of 12 healthy volunteers, simvastatin at the 80-mg dose had no effect on the metabolism of the probe cytochrome P450 isoform 3A4 (CYP3A4) substrates midazolam and erythromycin.
recorded 2026-08-30 · last checked 2026-09-04
Q14
Was Simvastatin studied with fasting and exercise?
fasting and exercise are named in Simvastatin's label sentences: "Twenty-four healthy participants were administered with a single oral dose of two 20 mg simvastatin tablets under fasting conditions, in a randomized, open-label, blind-endpoint analysis, two-way crossover study, with a washout period of one week." openfda-label+europepmc · 2026-08-30
2 recorded statements; fasting, exercise
Show the evidence
fasting
Twenty-four healthy participants were administered with a single oral dose of two 20 mg simvastatin tablets under fasting conditions, in a randomized, open-label, blind-endpoint analysis, two-way crossover study, with a washout period of one week.
exercise
Vitamin D-deficient T2DM patients aged 25-50 years performed moderate intensity aerobic exercise for 12 weeks and were randomized to receive simvastatin 40 mg daily, simvastatin 40 mg daily plus vitamin D 60 000 units once weekly, or vitamin D 60 000 units once weekly.
recorded 2026-08-30 · last checked 2026-09-04
Q15
What is recorded about Simvastatin and mTOR?
"We investigated whether simvastatin-induced metabolic stress enhances sensitivity to mTOR inhibition in a context-dependent manner in ccRCC." — where Simvastatin and mTOR appear together. Europe PMC · pathway abstract search · 2026-07-24
"We investigated whether simvastatin-induced metabolic stress enhances sensitivity to mTOR inhibition in a context-dependent manner in ccRCC."
PMID 42493660
"Mechanistically, simvastatin activated LKB1-AMPK signaling, suppressed AKT/mTOR activity, reduced glycolysis (↓pPFKFB2), increased FBP1 expression, and downregulated lipid biosynthesis enzymes (FASN, SCD), thereby promoting ER stress and apoptosis."
AMPKPMID 42493660
"Mechanistically, simvastatin activated LKB1-AMPK signaling, suppressed AKT/mTOR activity, reduced glycolysis (↓pPFKFB2), increased FBP1 expression, and downregulated lipid biosynthesis enzymes (FASN, SCD), thereby promoting ER stress and apoptosis."
mTORPMID 42493660
"Simvastatin-induced metabolic perturbation enhances mTOR inhibition in a cell-dependent manner, supporting dual metabolic targeting as a potential therapeutic strategy in ccRCC."
autophagy
PMID 42407178
"Furthermore, the review summarizes potential therapeutic strategies targeting macrophage autophagy, such as budesonide/simvastatin combination therapy and rapamycin derivatives, along with their clinical translation prospects, with the aim of providing a theoretical foundation for developing novel, autophagy-targeted precision therapies for allergic diseases."
"This study aimed to evaluate the possible ameliorative effect of two autophagy modulators, simvastatin and eugenol, on CP-related perturbations in an arginine-induced rat model."
PMID 41625333
"In wild-type mice, fasting-phase simvastatin activated SREBP-2-dependent autophagy, augmented PPARα signaling, and increased HDL cholesterol but impaired glucose homeostasis."
AMPK
PMID 39666279
"Moreover, inhibition of AMP-activated protein kinase (AMPK) and transient receptor potential vanilloid 1 (TRPV1) prevented simvastatin-induced activation of the autophagy-urea cycle pathway and NO production."
PMID 39666279
"Our findings suggest that simvastatin activates the autophagy-urea cycle pathway via TRPV1-AMPK signaling, which increases L-arginine bioavailability and ultimately promotes NO production in ECs."
recorded 2026-07-24 · last checked 2026-09-04
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