This page shows what was measured, who it was measured in, and what that does not settle.
What Carvedilol does in the body
A failing heart is drowned in adrenaline, and the adrenaline that keeps it beating hard today wears it out over years.
Carvedilol blocks the receptors adrenaline uses on heart muscle, so the heart beats slower and with less strain and the muscle stops being flogged. It also blocks a second kind of receptor on artery walls, so the arteries widen and the weakened heart has less resistance to push against. The first few weeks feel worse rather than better, because the heart temporarily loses support it had come to rely on.
Why people take it. A weakened heart and the months after a heart attack.
What happened in people
Among people with severe heart failure, carvedilol reduced deaths by about one third.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
Its metoprolol comparison used a shorter-acting form at a much lower daily dose than modern treatment.
Where it acts
Cardiac myocyte membrane and vascular smooth muscle — the beta-1 receptor on the heart and the alpha-1 receptor on the artery wall
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
Its recorded molecular formula is C24H26N2O4, weighing 406.5.
US prescribing information · fe462198-32ae-4f6c-befc-acb97fb017c9 · read 2026-08-30
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
A reviewer approved this sentence against this exact record and its sources.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 114 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.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
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.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
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.
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 severe chronic heart failure
35% risk reduction (95% CI 19 to 48), p=0.00013 unadjusted and p=0.0014 adjusted for interim analyses
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. Patients needing intensive care, with marked fluid retention, or on intravenous vasodilators or inotropes were excluded, so the result does not extend to decompensated failure.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 3.125, 6.25, 12.5 and 25 mg, taken twice daily; an extended-release capsule taken once daily also exists
Interval reported. 95% CI 19 to 48), p=0
Written into the record, not signed off as a reviewed claim.
Exercise capacity within each of four protocols; mortality was monitored across the programme rather than as a protocol primary endpoint
✗ The study did not show it
Who was studied
US Carvedilol Heart Failure Program (N Engl J Med 1996;334:1349-1355)
How many people
1094
Study design
Phase 3, four stratified double-blind placebo-controlled protocols analysed together
Compared against
A dummy treatment
Kind of result
Living longer, or avoiding a major event
What was found
Exercise endpoint not different from placebo in three of the four United States trials; programme-wide mortality 7.8% against 3.2%, a 65% risk reduction (95% CI 39 to 80), p<0.001
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. Terminated early by the Data and Safety Monitoring Board on the mortality signal. The 65% figure comes from pooling four differently designed protocols on an endpoint none of them was powered for, and the FDA advisory committee reached opposite conclusions on it at two separate meetings.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 3.125, 6.25, 12.5 and 25 mg, taken twice daily; an extended-release capsule taken once daily also exists
Interval reported. 95% CI 39 to 80), p<0
Written into the record, not signed off as a reviewed claim.
Mortality 34% against 40%, HR 0.83 (95% CI 0.74 to 0.93), p=0.0017; composite HR 0.94 (0.86 to 1.02), p=0.122
Repeated elsewhere
Unreplicated
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. One of the two co-primary endpoints was not met. The comparator was metoprolol tartrate 50 mg twice daily, not the succinate controlled-release 200 mg once daily used in MERIT-HF.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet at 3.125, 6.25, 12.5 and 25 mg, taken twice daily; an extended-release capsule taken once daily also exists
Interval reported. 95% CI 0
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 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
Heart: Beta-adrenoreceptor blocking activity reduces cardiac output in normal subjects and reduces exercise- and/or isoproterenol-induced tachycardia
US prescribing information · 010290af-81f4-0037-e063-6394a90a4638 · read 2026-08-27
Blood and vessels: Alpha-1-adrenoreceptor blocking activity causes vasodilation and reduces peripheral vascular resistance
US prescribing information · 010290af-81f4-0037-e063-6394a90a4638 · read 2026-08-27
Start
Carvedilol
What a person takes: Oral tablet at 3.125, 6.25, 12.5 and 25 mg, taken twice daily; an extended-release capsule taken once daily also exists.
The measurement behind this step
Taken with food, which slows absorption and reduces the orthostatic hypotension that follows a peak concentration. Extensive first-pass metabolism by CYP2D6 and CYP2C9 means exposure varies several-fold between people by genotype, and the label directs that discontinuation be spread over one to two weeks rather than stopped at once.
Getting in
A failing heart is soaked in adrenaline
When the pump weakens, the body reacts as though blood is being lost: it raises adrenaline, speeds the heart and tightens the arteries. That keeps blood pressure up today and destroys heart muscle over years.
╌╌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
Chronic sympathetic activation drives beta-1 receptor stimulation, calcium overload, myocyte apoptosis and adverse remodelling, along with renin release and salt retention. Circulating noradrenaline concentration is one of the strongest predictors of death in heart failure, which is the observation the whole beta-blocker programme was built on.
The tablet contains two mirror-image forms of the same molecule. One blocks the heart receptors. Both block the artery receptors. That is why it lowers blood pressure more than a plain beta-blocker.
╌╌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
Carvedilol is a racemate: non-selective beta-adrenoceptor blockade is present only in the S(-) enantiomer, while alpha-1 adrenergic blockade is present in both R(+) and S(-) at equal potency. There is no intrinsic sympathomimetic activity, which distinguishes it from the partial agonists that failed in heart failure trials.
With the receptors blocked, adrenaline cannot reach the heart muscle. The rate falls, each beat costs less oxygen, and the muscle stops being driven past what it can sustain.
╌╌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
Beta-1 and beta-2 blockade reduces heart rate, contractility and myocardial oxygen demand, and over months reverses the downregulation of beta-1 receptors that chronic adrenergic drive produces. Ejection fraction typically rises after several months of treatment, having first fallen.
The second half of the molecule relaxes the arteries, so the weakened heart has less resistance to push blood against. This is also why the drug can make you dizzy when you stand.
──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
Alpha-1 blockade lowers systemic vascular resistance and afterload. The cost is postural hypotension: hypotension and postural hypotension occurred in 9.7% and syncope in 3.4% of mild-to-moderate heart failure patients in trials, against 3.6% and 2.5% on placebo.
For the first weeks the heart has lost support it had been leaning on, and people often feel more tired and more breathless. The benefit arrives months later.
╌╌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
Acute negative inotropy transiently reduces cardiac output, and worsening heart failure or fluid retention during up-titration is recognised in the label and managed by dose adjustment. The long-term effect is the opposite of the short-term effect, which is the reason the drug was contraindicated for thirty years.
The endpoint here is not a laboratory number. In the severe heart failure trial, a third fewer patients died on carvedilol than on the dummy tablet.
──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
COPERNICUS measured a 35% reduction in all-cause mortality in 2,289 patients (95% CI 19 to 48, p=0.00013) and a 24% reduction in death or hospitalisation. COMET measured 34% against 40% all-cause mortality against metoprolol tartrate over a mean 58 months (HR 0.83, p=0.0017).
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 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 chronic heart failure across the full severity range, adults with reduced ejection fraction after a myocardial infarction, and adults with high blood pressure. Not people in decompensated failure needing intravenous inotropes, and not people with asthma.
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.
What the label states about particular groups
On pediatric, the label states: “Effectiveness of carvedilol in patients younger than 18 years has not been established.”
US prescribing information · fe462198-32ae-4f6c-befc-acb97fb017c9 · read 2026-08-30
On older people, the label states: “Of the 765 subjects with heart failure randomized to carvedilol in U.S. clinical trials, 31% (235) were aged 65 years or older, and 7.3% (56) were aged 75 years or older.”
US prescribing information · fe462198-32ae-4f6c-befc-acb97fb017c9 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Available data regarding use of carvedilol in pregnant women are insufficient to determine whether there are drug-associated risks of adverse developmental outcomes.”
US prescribing information · fe462198-32ae-4f6c-befc-acb97fb017c9 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data on the presence of carvedilol in human milk, the effects on the breastfed infant, or the effects on milk production.”
US prescribing information · fe462198-32ae-4f6c-befc-acb97fb017c9 · read 2026-08-30
Where the result stopped carrying
The prespecified exercise endpoint was not different from placebo in three of the four United States registration trials
The FDA Cardiovascular and Renal Drugs Advisory Committee reviewed the dossier twice and reached opposite decisions
The composite endpoint in COMET, and the primary composite in CAPRICORN, were both missed
Bronchial asthma is an absolute contraindication after deaths from status asthmaticus following single doses
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 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 (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
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 at 3.125, 6.25, 12.5 and 25 mg, taken twice daily; an extended-release capsule taken once daily also exists
✎ 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
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Taken with food, which slows absorption and reduces the orthostatic hypotension that follows a peak concentration.
✎ 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. The rest of the recorded wording: Extensive first-pass metabolism by CYP2D6 and CYP2C9 means exposure varies several-fold between people by genotype, and the label directs that discontinuation be spread over one to two weeks rather than stopped at once.
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.
The recorded stepping schedule
What follows is the schedule printed on the label, recorded as it is written there. It is a record of what was done, not a recommendation.
US prescribing information · 010290af-81f4-0037-e063-6394a90a4638 · read 2026-08-27
Starting dose, for 2 weeks: 3.125 mg twice daily — Label-stated starting dose for heart failure
US prescribing information · 010290af-81f4-0037-e063-6394a90a4638 · read 2026-08-27
Successive intervals of at least 2 weeks: If tolerated, dose increased to 6.25, 12.5, and 25 mg twice daily — Label-stated up-titration for heart failure; lower doses are maintained when higher doses are not tolerated
US prescribing information · 010290af-81f4-0037-e063-6394a90a4638 · read 2026-08-27
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 in bronchial asthma and related bronchospastic conditions, where deaths from status asthmaticus have been reported after single doses; also in second- or third-degree AV block, sick sinus syndrome, severe bradycardia without a pacemaker, cardiogenic shock or decompensated failure requiring intravenous inotropes, and severe hepatic impairment. Bradycardia, hypotension and worsening heart failure or fluid retention occur during up-titration and are managed by dose reduction. In diabetes it may mask the adrenergic warning symptoms of hypoglycaemia and alter glucose levels.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
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 at 3.125, 6.25, 12.5 and 25 mg, taken twice daily; an extended-release capsule taken once daily also exists
✎ 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
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: Extensive first-pass metabolism by CYP2D6 and CYP2C9 means exposure varies several-fold between people by genotype, and the label directs that discontinuation be spread over one to two weeks rather than stopped at once.
No source is stored against this line.
What is recorded as being sold
245 products list this as an active ingredient in the United States drug directory. 245 of them contain it and nothing else.
FDA National Drug Code directory · 72888-037 · read 2026-08-29
They are sold as capsule, extended release, pellet, pellets, coated, extended release, powder and tablet, film coated, taken oral.
FDA National Drug Code directory · 72888-037 · read 2026-08-29
The regulator's established pharmacologic class for it is adrenergic alpha-antagonists [moa], adrenergic beta1-antagonists [moa] and adrenergic beta2-antagonists [moa].
FDA National Drug Code directory · 72888-037 · read 2026-08-29
123 published labels name it as an active ingredient. 123 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · fe462198-32ae-4f6c-befc-acb97fb017c9 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · fe462198-32ae-4f6c-befc-acb97fb017c9 · read 2026-08-29
Carvedilol is film-coated tablets at Tablets: 3.125 mg, 6.25 mg, 12.5 mg, 25 mg, recorded as prescription product; fda label in effect 2026-05-11 in the United States.
US prescribing information · 010290af-81f4-0037-e063-6394a90a4638 · read 2026-08-27
Recorded price in US: 0.01675–0.03211 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 78 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.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Carvedilol 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 the 65% mortality reduction quoted from the United States programme came from a trial designed to measure mortality — it came from pooling four protocols whose own exercise endpoint failed
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 COMET showed carvedilol superior to the beta-blocker class, when the comparator was one salt of metoprolol at half the daily dose of the formulation with its own 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.
✗Goes past the evidence
That CAPRICORN showed a mortality benefit as its primary result, when its primary composite endpoint was not met
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 alpha-blocking component contributes to the survival benefit — it is a plausible mechanism, and no trial has isolated it
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 Carvedilol 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.
COPERNICUS: 35% fewer deaths in the sickest patients ever randomised to a beta-blocker
In plain words
Patients with symptoms at rest and a pumping fraction under a quarter — the group beta-blockers were supposed to be most dangerous in — were randomised to carvedilol or a dummy tablet. A third fewer died on the drug.
What was measured
All-cause mortality against placebo in severe heart failure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
COPERNICUS randomised 2,289 patients with symptoms of heart failure at rest or on minimal exertion, clinically euvolemic, with ejection fraction below 25%: 1,156 to carvedilol and 1,133 to placebo, for a mean of 10.4 months. There were 130 deaths on carvedilol against 190 on placebo, a 35% reduction in risk of death (95% CI 19 to 48, p=0.00013 unadjusted, p=0.0014 adjusted for interim analyses). Death or hospitalisation occurred in 425 against 507, a 24% reduction (95% CI 13 to 33, p<0.001). Fewer patients withdrew on carvedilol than on placebo (p=0.02). Patients requiring intensive care, with marked fluid retention, or on intravenous vasodilators or inotropes were excluded.
Written into the record, not signed off as a reviewed claim
COMET: fewer deaths than on metoprolol, over an average of five years
In plain words
Three thousand patients were randomised to carvedilol or to metoprolol and followed for nearly five years. Thirty-four percent of the carvedilol group died against forty percent of the metoprolol group. The combined measure of death or any hospital admission showed no difference.
What was measured
All-cause mortality and the composite of mortality or all-cause admission, carvedilol against metoprolol tartrate
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
COMET randomised 1,511 patients to carvedilol at a target of 25 mg twice daily and 1,518 to metoprolol tartrate at a target of 50 mg twice daily, in chronic heart failure with NYHA class II to IV, ejection fraction below 0.35 and a previous cardiovascular admission. Mean study duration was 58 months. All-cause mortality was 512 of 1,511 (34%) against 600 of 1,518 (40%), hazard ratio 0.83 (95% CI 0.74 to 0.93, p=0.0017), consistent across predefined subgroups. The co-primary composite of mortality or all-cause admission occurred in 1,116 (74%) against 1,160 (76%), hazard ratio 0.94 (95% CI 0.86 to 1.02, p=0.122) — not significant. Side effects and drug withdrawals did not differ much between groups.
Written into the record, not signed off as a reviewed claim
The registration programme failed its own prespecified endpoint
In plain words
The four American trials were designed around how far patients could exercise. In three of them exercise was no better on carvedilol than on placebo. The drug was approved on a death count that was collected across the whole programme rather than being any one trial primary question.
What was measured
Prespecified exercise endpoint, which was not different from placebo in three of four United States trials
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Fisher summarises the record: carvedilol did not meet the FDA two-positive-trial paradigm, because an exercise endpoint was not statistically different from placebo in three of the four United States trials. Most other endpoints were highly significant, and death, which was monitored across the whole United States programme rather than as a single trial primary endpoint, differed at p<0.0001. In the pooled programme of 1,094 patients, mortality was 7.8% on placebo against 3.2% on carvedilol, a 65% risk reduction (95% CI 39 to 80, p<0.001), which led the Data and Safety Monitoring Board to recommend early termination. The number quoted for this drug ever since — a 65% mortality reduction — comes from an analysis across four differently designed protocols, terminated early, that no individual trial was powered to make.
Written into the record, not signed off as a reviewed claim
The same advisory committee looked at the same data twice and decided the opposite way
In plain words
The FDA expert committee reviewed carvedilol on two occasions and reached opposite conclusions. What changed was not the data but the argument about whether a death count collected outside the trial design can carry an approval.
What was measured
That the 1995 approval rested on trials designed to test survival — it rested on a cross-programme mortality analysis after the designed endpoint failed, and the committee split on whether that was sufficient
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The carvedilol dossier was evaluated twice by the Cardiovascular and Renal Drugs Advisory Committee of the FDA, and the two meetings produced opposite decisions. Fisher records the crux as the two-positive-trial paradigm: carvedilol failed the exercise endpoint that the trials were built on, while the mortality signal collected across the programme was extremely strong. His conclusion, published alongside a dissenting analysis in the same issue, is that the usual paradigm is very useful but not an absolute principle, and that control of the type I error rate should rarely be violated but must be considered in context. Carvedilol was approved in 1995 and its heart failure benefit was later confirmed by COPERNICUS and by CAPRICORN, which does not retrospectively make the 1995 evidence what it was not.
Written into the record, not signed off as a reviewed claim
CAPRICORN missed its primary endpoint and is quoted for a component of it
In plain words
In patients with a weakened heart after a heart attack, the main measure — dying or being admitted to hospital — was no better on carvedilol. Deaths alone were lower, and that is the number everyone quotes.
What was measured
Composite of all-cause mortality or cardiovascular hospital admission after myocardial infarction
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
CAPRICORN randomised 1,959 patients with proven acute myocardial infarction and ejection fraction at or below 40% to carvedilol or placebo. The primary endpoint, all-cause mortality or hospital admission for cardiovascular problems, occurred in 340 (35%) against 367 (37%), hazard ratio 0.92 (95% CI 0.80 to 1.07) — no difference. All-cause mortality alone was lower: 116 (12%) against 151 (15%), hazard ratio 0.77 (95% CI 0.60 to 0.98, p=0.03). Cardiovascular mortality and non-fatal reinfarction were also lower. A trial that misses its primary endpoint and hits a component of it is hypothesis-generating for that component, and CAPRICORN is routinely cited as though the mortality result were the primary finding.
Written into the record, not signed off as a reviewed claim
COMET compared carvedilol against a metoprolol that no mortality trial ever used
In plain words
Carvedilol beat metoprolol in a head-to-head trial. The metoprolol used was a short-acting salt at fifty milligrams twice a day. The metoprolol with its own survival trial is a different salt, in a slow-release form, at four times that daily dose.
What was measured
That carvedilol is superior to the beta-blocker class rather than to one dose of one salt of one member of it — an inference the trial design cannot support
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
COMET used metoprolol tartrate at a target of 50 mg twice daily. MERIT-HF, the trial that established metoprolol in heart failure, used metoprolol succinate controlled-release at a target of 200 mg once daily in 3,991 patients and reported all-cause mortality of 7.2% per patient-year against 11.0% on placebo (RR 0.66, 95% CI 0.53 to 0.81, p=0.00009). Whether COMET demonstrated that carvedilol is superior to metoprolol, or that 100 mg of tartrate daily is inferior to 200 mg of succinate daily, cannot be settled from COMET, and the trial that would settle it has not been run. The COMET authors state their results suggest carvedilol extends survival compared with metoprolol; the comparator dose is the reason that sentence has been argued about ever since.
Written into the record, not signed off as a reviewed claim
A contraindication that has killed people
In plain words
Carvedilol blocks the receptors that keep airways open as well as the ones on the heart. In asthma that is not a caution, it is a bar: the label records deaths from status asthmaticus after single doses.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Bronchial asthma and related bronchospastic conditions are an absolute contraindication, and the label states that deaths from status asthmaticus have been reported following single doses of carvedilol. Other contraindications are second- or third-degree AV block, sick sinus syndrome, severe bradycardia without a pacemaker, cardiogenic shock or decompensated failure requiring intravenous inotropes, and severe hepatic impairment. In trials, bradycardia occurred in about 2% of hypertensive patients, 9% of heart failure patients and 6.5% of post-infarction patients; hypotension and postural hypotension in 9.7% and syncope in 3.4% of mild-to-moderate heart failure patients, against 3.6% and 2.5% on placebo. In diabetes the drug can mask the adrenergic warning symptoms of hypoglycaemia.
Source
Carvedilol United States prescribing information, Contraindications section 4 and Warnings and Precautions 5.1 to 5.6 (NDA 020297)
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
123 documents were read for this substance.
RNAWiki source record
111 of them state the same halfLife, and they agree.
RNAWiki source record
123 of them state the same bioavailability, and they agree.
RNAWiki source record
12 of them state the same tMax, and they agree.
RNAWiki source record
123 of them state the same volumeOfDistribution, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
0K47UL67F2
CAS registry number
72956-09-3
PubChem compound
2585
RxNorm concept
20352
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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
21 approved applications cover products containing this substance. The earliest was NDA020297, approved 19950914 to WAYLIS THERAP.
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What is not here
7 questions this page could not answer
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Felt, measured, or meaningful — found nothing in the sources checked.
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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 non-selective beta-blocker that also blocks the alpha-1 receptor, which cut deaths by 35% in 2,289 patients with severe heart failure in COPERNICUS and beat metoprolol tartrate on mortality in COMET — and which reached the United States market despite failing its prespecified exercise endpoint in three of four registration trials, on a mortality signal that no single trial had been designed to test.
Recorded evidence blocks (11)
Q1
On the Carvedilol label: indicated for what?
"Carvedilol tablets are an alpha/beta-adrenergic blocking agent indicated for the treatment of: mild to severe chronic heart failure ( 1.1 ) left ventricular dysfunction following myocardial infarction in clinically stable patients( 1.2 ) hypertension( 1.3 ) 1.1 Heart Failure Carvedilol tablets are indicated for the…": indications and usage on Carvedilol's label. DailyMed label · 8a82149f-aade-2a9b-e053-2995a90a9daf · 2026-08-26
Q2
175 registered trials of Carvedilol — at which phases?
Registered studies posting no result
136 of 175
175 registered studies of Carvedilol: 59 phase4, 33 na, 28 phase2, 27 phase3, 24 phase1, 8 na or unstated, 5 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
711 with a PubMed record
Show the evidence
phase4
59
na
33
phase2
28
phase3
27
phase1
24
na or unstated
8
9 more recorded rows
early phase1
5
completed
85
unknown
43
recruiting
16
terminated
11
withdrawn
10
active not recruiting
5
not yet recruiting
3
enrolling by invitation
2
recorded 2026-09-01 · last checked 2026-09-04
Q3
19 of Carvedilol's trials stopped: futility/efficacy, accrual/recruitment, funding/business, other?
futility/efficacy (1), accrual/recruitment (6), funding/business (5) and other (7): Carvedilol's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"In order to join forces with another study already running which aims to answer the same question."; 19 of 175 registered studies
Show the evidence
Trial
NCT00384566
withdrawn; "In order to join forces with another study already running which aims to answer the same question."
NCT00442923
withdrawn; "This study was withdrawn for lack of progress. No subjects were recruited."
NCT00444834
terminated; "IMP supply"
NCT00524134
terminated; "PI left the institution."
NCT00589303
terminated; "Lack of funding"
NCT01383044
terminated; "slow enrollment"
13 further recorded trials
NCT01659346
withdrawn; "Due to high mortality"
NCT01723371
withdrawn; "Due to lack of enrollment."
NCT02066649
withdrawn; "We need to revise and redesign the study"
NCT02120339
terminated; "Low enrollment"
NCT02357004
withdrawn; "Change in priority of interventional protocols"
NCT02507011
terminated; "Recruitment"
NCT03538015
terminated; "Sponsor was impacted by COVID-19 and did not have sufficient funds to continue."
NCT03861598
terminated; "Due to Covid"
NCT03879629
terminated; "slow accrual; insufficient funding to continue to accrue"
NCT03980249
withdrawn; "No funding"
NCT04121299
withdrawn; "lack of funding"
NCT04190433
withdrawn; "Administratively closed due to low/no accrual"
NCT06844669
terminated; "Futility"
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Carvedilol used Carvedilol 25 mg — over how long?
Human studies of Carvedilol used "Carvedilol 25 mg". ClinicalTrials.gov · 2026-09-01
20 recorded entries; human; capsule, tablet; also "Carvedilol 50 mg", "Carvedilol Tablets 12.5 mg", "Coreg® Tablets 12.5 mg"
7 to 10 hours; Following oral administration, the apparent mean terminal elimination half-life of carvedilol generally ranges from 7 to 10 hours.
bioavailabilitypharmacokinetics
25 %; Carvedilol tablets are rapidly and extensively absorbed following oral administration, with absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism.
metabolismpharmacokinetics
Carvedilol tablets are rapidly and extensively absorbed following oral administration, with absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism.
recorded 2026-08-26 · last checked 2026-09-04
Q6
Which running trial of Carvedilol could settle lifespan?
NCT06836856 measures Incidence of In-hospital mortality, reading out 2025-06.
4 open trials; n 100; "Evaluating the Impact of Adjuvant Use of Beta Blockers on Clinical Outcomes in Patients With Traumatic Brain Injury"
Show the evidence
Trial
NCT06836856
"Evaluating the Impact of Adjuvant Use of Beta Blockers on Clinical Outcomes in Patients With Traumatic Brain Injury"; n 100; "Incidence of In-hospital mortality"; 2025-06
NCT06977685
"Effect of Non-Selective Beta-Blockers on Outcomes in Cirrhosis Patients After Hospitalization: A Retrospective Cohort Using Target Trial Design"; n 7725; "All-cause mortality"; 2025-12-31
NCT04996550
"Are Carvedilol and Metoprolol Succinate Comparable Treatments in Heart Failure Patients With Reduced Ejection Fraction"; n 5600; "A combined endpoint of all-cause mortality or first hospitalization for worsening heart failure."; 2028-12-18
NCT03778554
"Danish Trial of Beta Blocker Treatment After Myocardial Infarction Without Reduced Ejection Fraction"; n 2760; "A composite of all-cause mortality, recurrent MI, revascularisation with PCI or CABG, ischemic stroke, incident heart failure, or malignant ventricular arrhythmia including resuscitated cardiac arrest of cardiac origin."; 2035-12-10
Q7
Which 46 trials of Carvedilol posted no result?
Posted no result
46 of 46 completed trials
Registrations
NCT00000294, NCT02832089, NCT01064154, NCT01064180, NCT00775619 and NCT00776113, and 40 more
Completion dates
oldest 2001-12; newest 2024-06-03
Show the evidence
Trial
NCT00000294
2001-12
NCT02832089
2002-03
NCT01064154
2002-05
NCT01064180
2002-05
NCT00775619
2003-12
NCT00776113
2003-12
14 further recorded trials
NCT00060918
2004-04
NCT00060931
2004-04
NCT00648622
2004-04
NCT00650416
2004-04
NCT01261065
2005-10
NCT00864149
2005-11
NCT00864435
2005-11
NCT00129363
2006-01
NCT00052026
2006-07
NCT00272805
2006-07
NCT00552708
2007-12
NCT00556920
2007-12
NCT00537043
2008-01
NCT03370835
2008-06
Q8
At the median, Carvedilol's trials enrolled 70 people — anything larger?
Median enrolment
70
Largest enrolment
22213
Registered trials counted
174
Q9
What do 76 spontaneous reports say about Carvedilol — 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.
Carvedilol appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 76 reaction mentions were counted: fatigue 17; nausea 17; dizziness 13; blood pressure increased 8. FAERS via Open Targets · CHEMBL1201167 · 2026-06-24
Show the evidence
fatigue
17
nausea
17
dizziness
13
blood pressure increased
8
blood pressure decreased
5
head injury
4
4 more recorded rows
heart rate decreased
4
pharmaceutical product complaint
4
gingival hyperplasia
2
nonspecific reaction
2
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Carvedilol's label not list?
( 7.8 ) 7.1 CYP2D6 Inhibitors and Poor Metabolizers Interactions of carvedilol with potent inhibitors of CYP2D6 isoenzyme (such as quinidine, fluoxetine, paroxetine, and propafenone) have not been studied, but these drugs would be expected to increase blood levels of the R(+) enantiomer of carvedilol [ see Clinical Pharmacology ( 12.3 ) ].
drug_interactions
7.6 Amiodarone Amiodarone, and its metabolite desethyl amiodarone, inhibitors of CYP2C9, and P-glycoprotein increased concentrations of the S(-) enantiomer of carvedilol by at least 2 fold [ see Clinical Pharmacology ( 12.5 ) ].
drug_interactions
The concomitant administration of amiodarone or other CYP2C9 inhibitors such as fluconazole with carvedilol may enhance the β-blocking properties of carvedilol resulting in further slowing of the heart rate or cardiac conduction.
pharmacokinetics
The primary P450 enzymes responsible for the metabolism of both R(+) and S(-)-carvedilol in human liver microsomes were CYP2D6 and CYP2C9 and to a lesser extent CYP3A4, 2C19, 1A2, and 2E1.
pharmacokinetics
CYP2D6 is thought to be the major enzyme in the 4'- and 5'-hydroxylation of carvedilol, with a potential contribution from 3A4.
pharmacokinetics
CYP2C9 is thought to be of primary importance in the O-methylation pathway of S(-)-carvedilol.
2 more recorded rows
Interaction statementpharmacokinetics
Carvedilol is subject to the effects of genetic polymorphism with poor metabolizers of debrisoquin (a marker for cytochrome P450 2D6) exhibiting 2- to 3-fold higher plasma concentrations of R(+)-carvedilol compared with extensive metabolizers.
Interaction statementpharmacokinetics
In contrast, plasma levels of S(-)-carvedilol are increased only about 20% to 25% in poor metabolizers, indicating this enantiomer is metabolized to a lesser extent by cytochrome P450 2D6 than R(+)-carvedilol.
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
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