This page shows what was measured, who it was measured in, and what that does not settle.
What Rofecoxib does in the body
Blood vessel walls make a substance that keeps platelets from sticking together.
Platelets themselves make a substance that makes them stick. Ordinary painkillers suppress both. Rofecoxib suppressed only the one the vessel wall makes, because that one comes from COX-2 and the platelet one comes from COX-1. The result was a slight tilt of the blood towards clotting, in a drug taken daily for years by people whose arteries were already narrowed.
Why people take it. Arthritis and pain relief, from a painkiller designed to spare the stomach
What happened in people
Confirmed upper gastrointestinal events halved against naproxen, 2.1 versus 4.5 per 100 patient-years in 8,076 patients
✎ 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 naproxen cardioprotection explained the VIGOR myocardial infarction gap — the measured naproxen effect in observational data is about 14%, not 400%
Where it acts
Vascular endothelium and inflamed synovium; COX-2 in endothelial cells
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 · 0QTW8Z7MCR · read 2026-08-29
Its recorded molecular formula is C17H14O4S, weighing 314.4.
PubChem record · 5090 · read 2026-08-29
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 103 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.
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.
Receptor
A receptor is a part of a cell that a signal fits into.
A picture of it, and where the picture fails
A receptor is like a lock waiting for one key.
Where that stops being true. A lock either opens or does not. A receptor can be half-triggered, or worn out.
What people get wrong. Fitting a receptor is read as causing a benefit. It causes a step, and nothing more.
A protein that binds a specific ligand and converts that binding into a cellular response.
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 2 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
Pain
∅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.
…Waiting for a reviewer1 registered symptom measure.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅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
Pain
visual analogue scale pain intensity
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.
… Waiting for a reviewer
1 registered symptom measure.
— Not recorded
Harms were not a registered measure for this goal.
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.
Confirmed clinical upper gastrointestinal events over a median 9.0 months, rofecoxib 50 mg versus naproxen 1000 mg daily
✓ The study showed what it set out to show
Who was studied
VIGOR (Vioxx Gastrointestinal Outcomes Research)
How many people
8076
Study design
Phase 4 randomised outcomes trial
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
RR 0.5 (95% CI 0.3 to 0.6), P < 0.001
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. Myocardial infarction 0.4% on rofecoxib versus 0.1% on naproxen was reported in the paper but attributed to naproxen cardioprotection. The journal later stated in an Expression of Concern that three myocardial infarctions in the rofecoxib arm were absent from the submitted manuscript.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet and oral suspension, once daily (12.5, 25 and 50 mg)
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Adenoma recurrence RR 0.76 (0.69 to 0.83), P < 0.0001; thrombotic events RR 1.92 (1.19 to 3.11), P = 0.008
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. Congestive heart failure, pulmonary oedema and cardiac failure were not adjudicated and separated at about five months with a hazard ratio of 4.61 (1.50 to 18.83).
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet and oral suspension, once daily (12.5, 25 and 50 mg)
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 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 eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
□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 lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.1 registered measure of this kind.
□A number that stands in for healthNo evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.No registered study measures this.
■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 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.
Start
Rofecoxib
What a person takes: Oral tablet and oral suspension, once daily (12.5, 25 and 50 mg).
The measurement behind this step
Once-daily oral dosing with roughly 93% bioavailability and a 17-hour half-life. The 50 mg strength was licensed for acute pain and short-term use, and was the dose used continuously for months in VIGOR.
Getting in
Swallowed once a day and absorbed almost completely
A tablet taken once daily. It stays in the body long enough that one dose covers a full day.
╌╌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
Oral bioavailability approximately 93% at 12.5 to 50 mg. Elimination half-life around 17 hours, which supports once-daily dosing and means the COX-2 blockade is continuous rather than intermittent.
Reaches inflamed joint tissue and the lining of blood vessels
It spreads into the inflamed joint, where it relieves pain, and also into the walls of blood vessels, where the trouble started.
╌╌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
Distributes into synovial tissue and vascular endothelium. COX-2 is inducible in inflamed synovium, which is the therapeutic target, but it is also constitutively expressed in endothelial cells, which is the off-target site that determined the outcome.
Occupies the COX-2 side pocket that COX-1 does not have
COX-2 has a small extra cavity that its cousin COX-1 lacks. A bulky part of the molecule fits into it, so the drug sticks to one enzyme and not the other.
╌╌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
The methylsulfonyl group binds the hydrophilic side pocket created by the Val523-for-Ile523 substitution in COX-2. COX-1, with the bulkier isoleucine, cannot accommodate it. This single-residue difference is the entire structural basis of coxib selectivity.
Vessel walls stop making the substance that keeps platelets apart. Platelets carry on making the substance that makes them stick. The balance tips towards clotting.
╌╌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
Endothelial COX-2 supplies most systemic prostacyclin (PGI2), an inhibitor of platelet aggregation and a vasodilator. Platelet thromboxane A2 comes from COX-1 and is untouched. Urinary metabolite studies in humans show suppression of the prostacyclin metabolite with no change in the thromboxane metabolite, leaving unopposed prothrombotic tone.
The stomach protection was real and measured. So was the extra rate of heart attacks and strokes. Both were in the trial data.
──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
Measured endpoints, not mechanism: 2.1 versus 4.5 confirmed upper gastrointestinal events per 100 patient-years in VIGOR, and 1.50 versus 0.78 adjudicated thrombotic events per 100 patient-years against placebo in APPROVe.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 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.
visual analogue scale pain intensity
Measured
Things only a test, a scale or a device shows.
No registered study measured anything of this kind.
Meaningful
Things that change how a life goes, not only a number.
No registered study measured anything of this kind.
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 (1)
international normalized
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.
Nobody now. Between 1999 and 2004 it was taken by an estimated 80 million people worldwide, mostly for osteoarthritis, and disproportionately by exactly the older population most exposed to cardiovascular risk.
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.
Where the result stopped carrying
The drug was withdrawn worldwide on 30 September 2004 after its own placebo-controlled trial was stopped early for cardiovascular events
Cumulative meta-analysis showed the randomised evidence reached RR 2.30 (1.22 to 4.33) by the end of 2000, four years before withdrawal
The New England Journal of Medicine issued and then reaffirmed an Expression of Concern about the pivotal publication
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
Withdrawn
❝ 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 and oral suspension, once daily (12.5, 25 and 50 mg)
✎ 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: S8.
No source is stored against this line.
What is in the pack
Once-daily oral dosing with roughly 93% bioavailability and a 17-hour half-life. The 50 mg strength was licensed for acute pain and short-term use, and was the dose used continuously for months in VIGOR.
✎ 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
Withdrawn worldwide on 30 September 2004 for thrombotic cardiovascular events. The measured harms are an adjudicated thrombotic event rate of 1.50 versus 0.78 per 100 patient-years against placebo, a congestive heart failure hazard ratio of 4.61 in the same trial, and a dose-dependent excess of serious coronary heart disease in cohort data. The gastrointestinal benefit that justified the drug was equally real and is not in dispute.
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.
Rofecoxib appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 20297 reaction mentions were counted. One report can name several reactions.
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∅Nothing found in the sources checked
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 and oral suspension, once daily (12.5, 25 and 50 mg)
✎ 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
The 50 mg strength was licensed for acute pain and short-term use, and was the dose used continuously for months in VIGOR.
✎ 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.
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, withdrawn medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Rofecoxib 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 naproxen cardioprotection explained the VIGOR myocardial infarction gap — the measured naproxen effect in observational data is about 14%, not 400%
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 excess thrombotic risk only began after 18 months of continuous treatment, a subdivision the original paper was later corrected on
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 COX-2 selectivity implied general safety, when the same selectivity that spares gastric COX-1 also spares platelet thromboxane
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.
How much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
What would answer it
A stored source that records 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.
How fast does the body clear it?
The sources RNAWiki checked hold nothing for this field.
Why it matters. Without this, nothing on this page can say how long anything lasts.
What would answer it
A stored source that records 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 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 Rofecoxib 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.
VIGOR: the gastrointestinal benefit was real and it was large
In plain words
In 8,076 rheumatoid arthritis patients, serious stomach and bowel complications happened at half the rate on rofecoxib that they did on naproxen. The drug did the job it was designed for.
What was measured
Confirmed upper gastrointestinal events per 100 patient-years, rofecoxib versus naproxen
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Randomised, double-blind, 8,076 patients aged 50 or older (or 40 or older on long-term glucocorticoids) with rheumatoid arthritis, assigned to rofecoxib 50 mg daily or naproxen 500 mg twice daily. Over a median 9.0 months, confirmed upper gastrointestinal events occurred at 2.1 per 100 patient-years on rofecoxib against 4.5 on naproxen (RR 0.5, 95% CI 0.3 to 0.6, p<0.001). Complicated events — perforation, obstruction, severe bleeding — were 0.6 against 1.4 per 100 patient-years (RR 0.4, 95% CI 0.2 to 0.8, p=0.005). Rheumatoid arthritis efficacy was similar in both arms.
Written into the record, not signed off as a reviewed claim
The same trial reported a four-fold excess of myocardial infarction, in 2000
In plain words
The trial that proved the stomach benefit also reported that heart attacks were four times more common on rofecoxib. That was published in November 2000, four years before the drug was pulled.
What was measured
Myocardial infarction incidence, 0.4% rofecoxib versus 0.1% naproxen
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the VIGOR results section: "The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7)." Overall mortality and cardiovascular mortality were similar between arms. The finding was framed in the paper as naproxen lowering risk rather than rofecoxib raising it, and the trial had no placebo arm that could have distinguished the two readings.
Written into the record, not signed off as a reviewed claim
The naproxen-cardioprotection explanation was an inference, and it did not survive
In plain words
The heart attack difference was explained away as naproxen protecting the heart rather than rofecoxib damaging it. When someone finally measured how protective naproxen actually is, it was far too small to account for the gap.
What was measured
That naproxen was cardioprotective enough to explain the VIGOR myocardial infarction difference, so rofecoxib carried no thrombotic risk of its own
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Jüni et al. pooled 18 randomised trials and 11 observational studies of rofecoxib and of naproxen. The combined observational estimate for naproxen against remote NSAID use was a relative risk of 0.86 (95% CI 0.75 to 0.99) — a roughly 14% reduction, which cannot generate the four-fold VIGOR gap. They also found little evidence that rofecoxib's relative risk varied by comparator arm (placebo, non-naproxen NSAID or naproxen; p=0.41) or by trial duration (p=0.82). Graham's Kaiser Permanente cohort reached the same conclusion from the other direction: naproxen versus remote NSAID use gave an adjusted odds ratio of 1.14 (1.00 to 1.30), not below 1.
Written into the record, not signed off as a reviewed claim
APPROVe: placebo-controlled, and the relative risk was 1.92
In plain words
A three-year trial against a dummy pill found nearly twice the rate of clots, heart attacks and strokes on rofecoxib. This is the result that ended the drug.
What was measured
Adjudicated thrombotic cardiovascular events per 100 patient-years versus placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Multicentre, randomised, double-blind, placebo-controlled; 2,586 patients with a history of colorectal adenomas assigned to rofecoxib 25 mg daily (n=1,287) or placebo (n=1,299). Confirmed thrombotic events, adjudicated blind by an external committee: 46 events in 3,059 patient-years on rofecoxib (1.50 per 100 patient-years) against 26 in 3,327 patient-years on placebo (0.78 per 100 patient-years), relative risk 1.92 (95% CI 1.19 to 3.11, p=0.008). Non-adjudicated congestive heart failure, pulmonary oedema and cardiac failure separated earlier, at about five months, with a hazard ratio of 4.61 (95% CI 1.50 to 18.83). Overall and cardiovascular mortality were similar. Merck withdrew rofecoxib worldwide on 30 September 2004.
Written into the record, not signed off as a reviewed claim
The chemoprevention endpoint APPROVe was actually designed to test was met
In plain words
APPROVe was not a heart study. It was testing whether rofecoxib prevented bowel polyps from coming back, and it did — recurrence fell from 55% to 41%.
What was measured
Adenoma recurrence over three years, 41% versus 55%
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the modified intention-to-treat analysis of 2,587 randomised subjects with a recent history of histologically confirmed adenomas, adenoma recurrence over three years was 41% on rofecoxib against 55% on placebo (RR 0.76, 95% CI 0.69 to 0.83, p<0.0001), with a reduction in advanced adenomas as well (p<0.01). The effect was larger in year one (RR 0.65, 0.57 to 0.73) than in years two and three (RR 0.81, 0.71 to 0.93). The authors' own conclusion was that rofecoxib significantly reduced adenoma risk "but also had serious toxicity". Both halves are the result.
Written into the record, not signed off as a reviewed claim
The evidence was statistically sufficient by the end of 2000
In plain words
Someone went back and added the trials up in the order they were published. By December 2000 the risk was already clear at conventional significance. The drug came off the market in September 2004.
What was measured
Cumulative pooled relative risk of myocardial infarction by calendar date of evidence
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Jüni et al. ran a cumulative random-effects meta-analysis with myocardial infarction as the primary endpoint. By the end of 2000, across 52 myocardial infarctions in 20,742 patients, the pooled relative risk from randomised trials was 2.30 (95% CI 1.22 to 4.33, p=0.010). One year later, at 64 events in 21,432 patients, it was 2.24 (1.24 to 4.02, p=0.007). Their stated interpretation: "rofecoxib should have been withdrawn several years earlier." The paper is not a new dataset; it is the existing dataset read in chronological order, which is the part nobody was doing.
Written into the record, not signed off as a reviewed claim
The New England Journal issued an Expression of Concern about its own VIGOR paper
In plain words
Five years after publishing the trial, the journal said three heart attacks had been deleted from the manuscript before it went to press, and that the editors only learned of it during litigation.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In December 2005 the editors published an Expression of Concern regarding Bombardier et al. It stated that three myocardial infarctions in the rofecoxib group were not included in the version submitted for publication, that the editors had learned this from materials disclosed in litigation, and that the omission made the difference between the arms appear smaller than it was. The Expression of Concern was reaffirmed in 2006 after the authors' response. The trial's gastrointestinal conclusion was not retracted; the cardiovascular table was the disputed part.
Written into the record, not signed off as a reviewed claim
Kaiser Permanente: 1.59-fold risk against celecoxib, 3.58-fold above 25 mg daily
In plain words
An FDA scientist matched every serious heart event in a 1.4-million-person health plan against controls. Rofecoxib carried more risk than celecoxib, and the high dose carried three and a half times as much.
What was measured
Adjusted odds ratio for acute myocardial infarction and sudden cardiac death versus celecoxib
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Nested case-control study within a Kaiser Permanente California cohort of all patients aged 18 to 84 treated with an NSAID between 1 January 1999 and 31 December 2001. Over 2,302,029 person-years, 8,143 cases of serious coronary heart disease occurred, 2,210 of them (27.1%) fatal; each case was risk-set matched to four controls. Multivariate adjusted odds ratios against celecoxib: rofecoxib all doses 1.59 (95% CI 1.10 to 2.32, p=0.015); rofecoxib 25 mg/day or less 1.47 (0.99 to 2.17, p=0.054); rofecoxib above 25 mg/day 3.58 (1.27 to 10.11, p=0.016). The dose-response is the part that matters, because VIGOR used 50 mg.
Written into the record, not signed off as a reviewed claim
The claim that risk only appeared after 18 months rested on a fragile analysis
In plain words
The trial report said the danger did not start until a year and a half in. That reassurance came from a statistical test that the journal itself later revisited, and the original paper was corrected.
What was measured
That rofecoxib was cardiovascularly safe for the first 18 months of continuous use, so short courses carried no excess risk
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The APPROVe report stated that the increased relative risk "became apparent after 18 months of treatment" and that event rates were similar during the first 18 months. PubMed records an erratum to the paper at N Engl J Med 2006;355:221. The journal separately published a methodological Perspective, Lagakos, "Time-to-Event Analyses for Long-Term Treatments — The APPROVe Trial", examining the time-to-event methods behind that delayed-effect claim. The point is narrow and worth stating precisely: the 1.92 relative risk over the whole trial is the robust result, and the reassuring subdivision of it in time is the part that was not.
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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.
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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.
A COX-2 selective anti-inflammatory that did exactly what it was designed to do to the stomach, showed a five-fold myocardial infarction excess in its own pivotal safety trial in 2000, and stayed on the market for four more years while that finding was attributed to the comparator drug.
Recorded evidence blocks (8)
Q2
What did Rofecoxib's largest trial (15000 people) and its longest (6.6 years) measure?
15000 people in Rofecoxib's largest registered study, 6.6 years in its longest registered window, measuring Maximum tolerated dose of VIOXX (rofecoxib) with 6 weeks of daily cranial radiation therapy. ClinicalTrials.gov · 2026-09-01
10 phase3, 4 phase2, 2 na, 2 phase4, 1 phase1; NCT00031863; 2007-09; no ageing endpoint recorded. Last human test completed 2009, NCT01762891.
Interpretation These counts include studies where Rofecoxib 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
10
phase2
4
na
2
phase4
2
phase1
1
Last recorded human testNCT01762891
2009-09
recorded 2026-09-01 · last checked 2026-09-04
Q3
From mouse to human: where has Rofecoxib shown lifespan?
"Unavailability of study drug."; 4 of 16 registered studies
Show the evidence
Trial
NCT00038389
terminated; "Unavailability of study drug."
NCT00657449
terminated; "See termination reason in detailed description."
NCT00844727
terminated; "Drug withdrawal"
NCT04684511
terminated; "Low enrollment. The termination of the trial was not based on any safety concerns in the study."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Which 10 trials of Rofecoxib posted no result?
Posted no result
10 of 10 completed trials
Registrations
NCT00568295, NCT00637949, NCT00004845, NCT00637988, NCT00026819 and NCT00263094, and 4 more
Completion dates
oldest 2000-10; newest 2009-09
Show the evidence
Trial
NCT00568295
2000-10
NCT00637949
2001-03
NCT00004845
2001-12
NCT00637988
2003-06
NCT00026819
2003-11
NCT00263094
2004-11
4 further recorded trials
NCT00060476
2004-12-08
NCT00385606
2006-07
NCT00031863
2007-09
NCT01762891
2009-09
Q6
At the median, Rofecoxib's trials enrolled 178 people — anything larger?
Median enrolment
178
Largest enrolment
15000
Registered trials counted
14
Q7
What do 20297 spontaneous reports say about Rofecoxib — 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.
Rofecoxib appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 20297 reaction mentions were counted: myocardial infarction 3173; coronary artery disease 2903; cerebrovascular accident 2655; hypertension 2628. open-targets-adr · CHEMBL122 · 2026-06-24
Show the evidence
myocardial infarction
3173
coronary artery disease
2903
cerebrovascular accident
2655
hypertension
2628
chest pain
2348
depression
1768
4 more recorded rows
dyspnoea
1289
acute myocardial infarction
1181
anxiety
1181
dizziness
1171
recorded 2026-06-24 · last checked 2026-09-04
Q8
Was Rofecoxib studied with fasting and exercise?
fasting and exercise are named in Rofecoxib's label sentences: "We performed a double-blind randomized prospective trial of rofecoxib 50 mg versus placebo, taken just prior to the onset of fasting, Yom Kippur 2004." openfda-label+europepmc · 2007-08-01
2 recorded statements; fasting, exercise
Show the evidence
fasting
We performed a double-blind randomized prospective trial of rofecoxib 50 mg versus placebo, taken just prior to the onset of fasting, Yom Kippur 2004.
exercise
To test the hypothesis that selective inhibition of cyclooxygenase (COX)-2 would result in exercise-induced platelet activation by causing a shift in the endogenous thromboxane (TX)/prostacyclin balance, a double blind, randomized study comparing aspirin (300 mg/d) with rofecoxib (25 mg/d) (cross-over design, 14 days washout between treatments) in n = 10 trained healthy volunteers was carried out.
recorded 2007-08-01 · last checked 2026-09-04
Q9
What is recorded about Rofecoxib and autophagy?
"Despite both DMSO and rofecoxib induced autophagy alone and in synergy, they reduced mitotic catastrophe and autophagy triggered by vinorelbine, which was also reflected by reduced inhibition of spheroid S-phase." — where Rofecoxib and autophagy appear together. Europe PMC · pathway abstract search · 2019-05-28
"Despite both DMSO and rofecoxib induced autophagy alone and in synergy, they reduced mitotic catastrophe and autophagy triggered by vinorelbine, which was also reflected by reduced inhibition of spheroid S-phase."
NAD+
PMID 15851630
"Rofecoxib and nimesulide produced significant antioxidative effect by reducing NAD(P)H oxidase-dependent superoxide generation."
PMID 14570773
"In contrast to microsomes, the oxidation of rofecoxib to 5-hydroxyrofecoxib by S9 fractions followed two pathways, one NADPH-dependent and one NAD+-dependent (non-cytochrome P450), with the latter accounting for about 40% of total activity."
recorded 2019-05-28 · last checked 2026-09-04
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