This page shows what was measured, who it was measured in, and what that does not settle.
What Digoxin does in the body
Sodium builds up inside the cell, which slows a second exchanger that normally removes calcium, so calcium accumulates and each contraction becomes stronger.
Every heart muscle cell runs a pump in its outer membrane that pushes sodium out and pulls potassium in. Digoxin jams that pump. Separately and probably more importantly, digoxin acts on the nervous system to increase vagal tone, which slows conduction through the electrical junction between the atria and the ventricles and brings a fast resting pulse down. The margin between a useful dose and a toxic one is narrower than for almost any other common drug.
Why people take it. Heart failure symptoms, and slowing a fast resting pulse in long-standing atrial fibrillation
What happened in people
Crude mortality in DIG men by serum concentration band: 29.9% at 0.5 to 0.8 ng/mL, 38.8% at 0.9 to 1.1, 48.0% at 1.2 or above (p=0.006 for trend)
✎ 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 digoxin prolongs life in heart failure — measured directly and found not to
Where it acts
The cardiac myocyte membrane and the atrioventricular node — the sodium pump on the outside of the heart muscle cell, and the conduction tissue it slows indirectly through the vagus nerve
Kind of result
A step measured inside a person
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 · 73K4184T59 · read 2026-08-29
Its recorded molecular formula is C41H64O14, weighing 780.95.
US prescribing information · 28f2c2cd-e58c-aea2-e063-6394a90a73e7 · 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.
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 152 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 patients with heart failure and left ventricular ejection fraction 0.45 or below, on diuretics and ACE inhibitors
✗ The study did not show it
Who was studied
DIG — Digitalis Investigation Group main trial (N Engl J Med 1997;336:525-533)
1,181 deaths (34.8%) on digoxin against 1,194 (35.1%) on placebo; risk ratio 0.99 (95% CI 0.91 to 1.07), p=0.80, over an average 37 months
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Hospitalisation for worsening heart failure did fall, 26.8% against 34.7%, RR 0.72 (95% CI 0.66 to 0.79), p<0.001. Death from worsening heart failure trended down (RR 0.88, p=0.06) while total deaths did not move, which implies an offsetting rise in other cardiac deaths. Two later post-hoc analyses of this dataset found higher mortality in women on digoxin and a concentration-dependent mortality gradient, neither of which was a randomised comparison.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, oral solution and intravenous injection; paediatric formulations available
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Preservation of exercise capacity on continued digoxin against withdrawal to placebo over 12 weeks in NYHA class II to III heart failure previously treated with oral digoxin
✓ The study showed what it set out to show
Who was studied
RADIANCE and PROVED withdrawal trials (reported in the NDA 020405 label)
Both trials demonstrated better preservation of exercise capacity on continued LANOXIN, and continued treatment reduced heart-failure-related hospitalisations, emergency care and the need for additional heart failure therapy
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. These are withdrawal designs in patients already established and tolerating the drug, which selects for responders and cannot answer whether starting digoxin in a new patient helps. They are 12 weeks long and measured no mortality endpoint. Sample size shown is the sum of the two trials the label describes, 178 and 88.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, oral solution and intravenous injection; paediatric formulations available
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Conversion of recent-onset atrial fibrillation to sinus rhythm, and ventricular rate control in chronic atrial fibrillation
✗ The study did not show it
Who was studied
Atrial fibrillation programme — conversion and rate control trials (NDA 020405 label)
How many people
315
Study design
Randomised, double-blind, placebo- and active-controlled
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Across three randomised double-blind trials totalling 315 adults, conversion was equally likely and equally rapid on digoxin and placebo. Digoxin reduced resting heart rate but not heart rate during exercise
Repeated elsewhere
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. In a separate randomised 120-patient trial against sotalol and amiodarone, digoxin had the lowest incidence of conversion to sinus rhythm and the least satisfactory rate control when conversion did not occur. The licensed indication is limited accordingly to control of resting ventricular rate in chronic atrial fibrillation.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, oral solution and intravenous injection; paediatric formulations available
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 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: By inhibiting Na-K ATPase, causes increased availability of intracellular calcium in the myocardium and conduction system, with consequent increased inotropy
US prescribing information · 03612934-62f4-4002-85af-6c66cd172acb · read 2026-08-27
Blood and vessels: Reduces catecholamine reuptake at nerve terminals, rendering blood vessels more sensitive to endogenous or exogenous catecholamines
US prescribing information · 03612934-62f4-4002-85af-6c66cd172acb · read 2026-08-27
Start
Digoxin
What a person takes: Oral tablet, oral solution and intravenous injection; paediatric formulations available.
The measurement behind this step
Cleared predominantly by the kidney, so renal function largely sets the maintenance dose, and the elimination half-life is measured in days rather than hours. That is why an adequate blood level takes about a week to establish without a loading strategy, and why a fall in renal function raises the level over the same timescale. The label directs obtaining serum digoxin concentrations immediately before the next scheduled dose or at least six hours after the last, and interpreting the number in the overall clinical context rather than using an isolated measurement to change the dose.
Getting in
A steroid with a lactone and three sugars
Digoxin comes from the leaves of woolly foxglove. Its business end is a small ring that latches onto a pump in the heart cell membrane; the sugar chain attached to it decides how long the drug stays in the body.
╌╌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
A cardenolide: steroid nucleus, unsaturated five-membered lactone at C17, three digitoxose sugars at C3. It differs from digitoxin by a single C12 hydroxyl, which redirects clearance from hepatic over weeks to renal over days.
Every cell runs a pump that pushes sodium out and pulls potassium in. Digoxin blocks it from the outside — at the same site potassium uses, which is why low potassium makes the drug stronger.
╌╌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 label states that all of digoxin’s actions are mediated through its effects on Na-K ATPase, the enzyme responsible for moving sodium out of and potassium into cells. Binding is at the extracellular face where potassium competes.
Calcium accumulates and the contraction gets stronger
With sodium building up inside, the exchanger that normally clears calcium out of the cell slows down. More calcium means a more forceful beat.
╌╌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 label states that inhibiting Na-K ATPase causes increased availability of intracellular calcium in the myocardium and conduction system, with consequent increased inotropy, increased automaticity and reduced conduction velocity — an increase in the force and velocity of systolic contraction.
Separately from the pump, digoxin increases vagal tone and resets pressure sensors, which slows conduction through the junction between the upper and lower chambers. That is what brings a fast resting pulse down.
╌╌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 label describes indirect parasympathetic stimulation of the autonomic nervous system with effects on the sinoatrial and atrioventricular nodes, reduced catecholamine reuptake at nerve terminals, and increased baroreceptor sensitisation with enhanced sympathetic withdrawal. At higher concentrations it increases central sympathetic outflow and allows efflux of intracellular potassium.
In heart failure the measurable result is fewer hospital stays and a better ability to walk, not a longer life.
──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
DIG: hospitalisation for worsening heart failure 26.8% against 34.7%, RR 0.72 (95% CI 0.66 to 0.79), p<0.001, with 6% fewer hospitalisations overall. RADIANCE and PROVED, the two withdrawal trials in 178 and 88 patients, showed better preservation of exercise capacity on continued digoxin.
The same trial found deaths of 34.8% on the drug and 35.1% on placebo. The label puts that finding inside the indication itself.
╌╌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
DIG: 1,181 deaths (34.8%) against 1,194 (35.1%), risk ratio 0.99 (95% CI 0.91 to 1.07), p=0.80, over an average 37 months. The LANOXIN heart failure indication states the drug improves ejection fraction, exercise capacity and hospitalisation "while having no effect on mortality".
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 heart failure symptoms persisting on a diuretic and an ACE inhibitor, adults needing resting rate control in chronic atrial fibrillation, and children with heart failure. Not people with ventricular fibrillation, and not people with Wolff-Parkinson-White syndrome who develop atrial fibrillation.
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: “The safety and effectiveness of digoxin in the treatment of heart failure in children have not been established in adequate and well-controlled studies.”
US prescribing information · 28f2c2cd-e58c-aea2-e063-6394a90a73e7 · read 2026-08-30
On older people, the label states: “The majority of clinical experience gained with digoxin has been in the elderly population.”
US prescribing information · 28f2c2cd-e58c-aea2-e063-6394a90a73e7 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Experience with digoxin in pregnant women over several decades, based on published retrospective clinical studies and case reports, has not led to the identification of a drug associated risk of major birth defects, miscarriage or adverse maternal and fetal outcomes.”
US prescribing information · 28f2c2cd-e58c-aea2-e063-6394a90a73e7 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary The digoxin dose received through breastfeeding is up to 4% of the neonatal maintenance dosage, which is unlikely to be clinically relevant.”
US prescribing information · 28f2c2cd-e58c-aea2-e063-6394a90a73e7 · read 2026-08-30
On people with reduced liver function, the label states: “Plasma digoxin concentrations in patients with acute hepatitis generally fall within the range of profiles in a group of healthy subjects.”
US prescribing information · 28f2c2cd-e58c-aea2-e063-6394a90a73e7 · read 2026-08-30
On people with reduced kidney function, the label states: “The clearance of digoxin can be primarily correlated with the renal function as indicated by creatinine clearance.”
US prescribing information · 28f2c2cd-e58c-aea2-e063-6394a90a73e7 · read 2026-08-30
Where the result stopped carrying
The mortality endpoint of the only adequately powered placebo-controlled trial, at p=0.80
Conversion of atrial fibrillation to sinus rhythm — no better than placebo in three randomised trials
Exercise heart rate control in atrial fibrillation, and the head-to-head comparison against sotalol and amiodarone
Post-hoc analyses of the trial dataset found higher mortality in women and at higher serum concentrations, in the direction of harm rather than benefit
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
Given by a clinician
❝ 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, oral solution and intravenous injection; paediatric formulations available
✎ 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: S1.
No source is stored against this line.
What is in the pack
Cleared predominantly by the kidney, so renal function largely sets the maintenance dose, and the elimination half-life is measured in days rather than hours.
✎ 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: That is why an adequate blood level takes about a week to establish without a loading strategy, and why a fall in renal function raises the level over the same timescale. The label directs obtaining serum digoxin concentrations immediately before the next scheduled dose or at least six hours after the last, and interpreting the number in the overall clinical context rather than using an isolated measurement to change the dose.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Contraindicated in ventricular fibrillation and in known hypersensitivity to digoxin or other digitalis preparations. In Wolff-Parkinson-White syndrome with atrial fibrillation, digoxin slows atrioventricular conduction more than accessory-pathway conduction and increases the risk of a rapid ventricular response leading to ventricular fibrillation. It may cause severe sinus bradycardia or sinoatrial block in pre-existing sinus node disease, and advanced or complete heart block in pre-existing incomplete AV block, so a pacemaker should be considered first. It is not recommended in acute myocardial infarction, should be avoided in myocarditis, and carries a risk of ventricular arrhythmias during electrical cardioversion. Toxicity presents as nausea, vomiting, visual disturbance and cardiac arrhythmias; advanced age, low body weight, impaired renal function and electrolyte abnormalities predispose to it. Levels below 0.5 ng/mL are associated with diminished efficacy and levels above 2 ng/mL with increased toxicity without increased benefit.
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, oral solution and intravenous injection; paediatric formulations available
✎ 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: That is why an adequate blood level takes about a week to establish without a loading strategy, and why a fall in renal function raises the level over the same timescale. The label directs obtaining serum digoxin concentrations immediately before the next scheduled dose or at least six hours after the last, and interpreting the number in the overall clinical context rather than using an isolated measurement to change the dose.
No source is stored against this line.
What is recorded as being sold
74 products list this as an active ingredient in the United States drug directory. 74 of them contain it and nothing else.
FDA National Drug Code directory · 71335-3156 · read 2026-08-29
They are sold as injection, injection, solution, powder, solution and tablet, taken intramuscular, intravenous, oral and parenteral.
FDA National Drug Code directory · 71335-3156 · read 2026-08-29
The regulator's established pharmacologic class for it is cardiac glycoside [epc] and cardiac glycosides [cs].
FDA National Drug Code directory · 71335-3156 · read 2026-08-29
44 published labels name it as an active ingredient. 44 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · dcf9b23b-5840-46ff-bb61-c57a02831a03 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · dcf9b23b-5840-46ff-bb61-c57a02831a03 · read 2026-08-29
42 marketed supplement labels list this ingredient, classed as botanical, non-nutrient/non-botanical and other combinations.
Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
Digoxin is scored tablets at Scored tablets: 125 mcg and 250 mcg, recorded as prescription product; fda label in effect 2024-09-04 in the United States.
US prescribing information · 03612934-62f4-4002-85af-6c66cd172acb · read 2026-08-27
Recorded price in US: 0.13243–8.52641 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 30 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
Recorded price in US: 1.13271 USD per one millilitre, across 3 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Digoxin 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 digoxin prolongs life in heart failure — measured directly and found not to
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 it provides rate control in atrial fibrillation generally, when the effect measured was on resting rate only
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 concentration-mortality gradient proves lowering a level saves lives, when serum concentration was observed rather than randomised
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 AFFIRM association proves digoxin causes death in atrial fibrillation, when patients were not randomised to it and sicker patients receive it more often
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 two centuries of clinical confidence constituted evidence of survival benefit before 1997
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 Digoxin 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.
The DIG trial: no effect on mortality, and the label says so in the indication
In plain words
Six thousand eight hundred people with heart failure were randomised to digoxin or placebo. Almost exactly the same proportion died in each group. Hospital admissions for heart failure fell substantially.
What was measured
All-cause mortality over an average 37 months in 6,800 patients with heart failure and ejection fraction 0.45 or below
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The DIG main trial randomised 6,800 patients with left ventricular ejection fraction of 0.45 or less to digoxin (n=3,397, median 0.25 mg daily) or placebo (n=3,403) on top of diuretics and ACE inhibitors, with average follow-up 37 months. There were 1,181 deaths (34.8%) on digoxin and 1,194 (35.1%) on placebo: risk ratio 0.99 (95% CI 0.91 to 1.07), p=0.80. Death attributed to worsening heart failure showed a non-significant trend downward (RR 0.88, 95% CI 0.77 to 1.01, p=0.06). Hospitalisation for worsening heart failure fell from 34.7% to 26.8%, RR 0.72 (95% CI 0.66 to 0.79), p<0.001, with 6% fewer hospitalisations overall. An ancillary trial in 988 patients with ejection fraction above 0.45 was consistent. What makes this record unusual is the regulatory consequence: the LANOXIN indication for heart failure now reads that the drug improves ejection fraction, exercise capacity and hospitalisation "while having no effect on mortality". A negative mortality finding written into an indication is rare, and it is the most honest sentence on the label.
Written into the record, not signed off as a reviewed claim
Two hundred and twelve years between the first description and the first trial
In plain words
Foxglove was written up as a treatment for dropsy in 1785. The first properly powered placebo-controlled trial of whether digoxin helps people live longer reported in 1997, and it did not.
What was measured
Interval between first published clinical description and first adequately powered placebo-controlled mortality trial
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
William Withering published his account of the foxglove and its medical uses in 1785. Digoxin was isolated from Digitalis lanata in 1930 and the injection was approved in the United States on 16 November 1954 under NDA 009330, before efficacy evidence was a condition of approval. The tablet received its own approval under NDA 020405 on 30 September 1997 — the same year the DIG trial reported. So the modern regulatory approval of the tablet and the first answer to the question of whether the drug prolongs life arrived within months of each other, after two centuries of continuous prescribing. The result was neutral on mortality and positive on hospitalisation, which is neither vindication nor refutation. It is what an unmeasured practice looks like once someone finally measures it, and the value of the record is that it shows how long a therapy can be used confidently without anyone knowing.
Written into the record, not signed off as a reviewed claim
For atrial fibrillation it controls the resting rate and not the exercise rate
In plain words
The label states plainly that digoxin reduced the resting heart rate but not the heart rate during exercise, and that in a head-to-head trial it gave the least satisfactory rate control of the three drugs tested.
What was measured
That digoxin provides rate control in atrial fibrillation generally, when its label records an effect on resting rate only and the worst performance of three drugs in a head-to-head comparison
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The LANOXIN clinical studies section reports that digoxin reduced resting heart rate but not heart rate during exercise. In three randomised double-blind trials totalling 315 adults comparing digoxin with placebo for conversion of recent-onset atrial fibrillation, conversion was equally likely and equally rapid in both groups — digoxin does not cardiovert. In a randomised 120-patient trial comparing digoxin, sotalol and amiodarone, patients randomised to digoxin had the lowest incidence of conversion to sinus rhythm and the least satisfactory rate control when conversion did not occur. The licensed indication is correspondingly precise: control of resting ventricular rate in adults with chronic atrial fibrillation. A patient whose pulse is acceptable in a clinic chair and unacceptable climbing stairs has been treated exactly as the label describes, and the label does not claim otherwise.
Source
LANOXIN (digoxin) United States prescribing information, sections 1.3 and 14.2 (NDA 020405)
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
The therapeutic range was moved downward by a re-analysis of the DIG data
In plain words
A re-analysis of the same trial found that men whose blood levels sat between 0.5 and 0.8 did better than placebo, and men whose levels were 1.2 or above did substantially worse. The target range came down as a result.
What was measured
All-cause mortality by serum digoxin concentration band against placebo in 3,782 men from the DIG trial
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Rathore and colleagues re-analysed DIG restricted to 3,782 men with ejection fraction 45% or below, dividing the digoxin arm by serum digoxin concentration at one month. Crude all-cause mortality rose across the bands: 29.9% at 0.5 to 0.8 ng/mL, 38.8% at 0.9 to 1.1 and 48.0% at 1.2 or above, p=0.006 for trend. Against placebo, the lowest band had a 6.3% lower absolute mortality (95% CI 2.1% to 10.5%), the middle band no reduction (2.6% increase, 95% CI −3.0% to 8.3%), and the highest band an 11.8% higher absolute mortality (95% CI 5.7% to 18.0%). Adjusted hazard ratios were 0.80, 0.89 and 1.16 against placebo. The current label reflects the shift: levels below 0.5 ng/mL are associated with diminished efficacy and levels above 2 ng/mL with increased toxicity without increased benefit, and the label directs that a concentration be interpreted in clinical context rather than used in isolation to change a dose. This is a post-hoc analysis of an observed rather than randomised variable, so it cannot prove that lowering a level saves a life. It is strong enough that practice moved, and the reader should know which of those two statements the evidence supports.
Written into the record, not signed off as a reviewed claim
In the same trial, women on digoxin died more often than women on placebo
In plain words
A post-hoc analysis found the drug behaved differently by sex: women randomised to digoxin had a higher death rate than women on placebo, while men showed no difference.
What was measured
All-cause mortality by sex in the DIG trial (women: adjusted HR 1.23, 95% CI 1.02 to 1.47; men: 0.93, 95% CI 0.85 to 1.02; interaction p=0.014)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Rathore, Wang and Krumholz analysed the 6,800 DIG participants for an interaction between sex and digoxin on all-cause mortality. The absolute difference between men and women in digoxin’s effect was 5.8 percentage points (95% CI 0.5 to 11.1), p=0.034 for interaction. Women on digoxin died at 33.1% against 28.9% on placebo — absolute difference 4.2%, 95% CI −0.5% to 8.8%. Men died at 35.2% against 36.9%, difference −1.6%, 95% CI −4.2% to 1.0%. In multivariable analysis digoxin carried an adjusted hazard ratio of 1.23 (95% CI 1.02 to 1.47) in women and 0.93 (95% CI 0.85 to 1.02) in men, interaction p=0.014. This is a post-hoc subgroup analysis and the confidence interval on the women’s absolute difference crosses zero, so it is a signal rather than a finding. It is also mechanistically coherent with the concentration analysis published the following year, since women in DIG achieved higher serum concentrations for a given dose. Two independent post-hoc analyses of the same trial pointing at the same explanation is worth more than either alone, and still less than a trial designed to test it.
Written into the record, not signed off as a reviewed claim
In atrial fibrillation, the mortality signal is observational and disputed
In plain words
An analysis of a large atrial fibrillation trial found people taking digoxin died more often, by about 40%. But they were not randomised to it, and sicker people are more likely to be given it in the first place.
What was measured
That digoxin causes the excess mortality observed in atrial fibrillation cohorts — an association from a non-randomised comparison within a randomised trial, adjusted but not randomised
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Whitbeck and colleagues analysed digoxin use within the AFFIRM trial using multivariable Cox models. Digoxin was associated with increased all-cause mortality (estimated hazard ratio 1.41, 95% CI 1.19 to 1.67, p<0.001), cardiovascular mortality (1.35, 95% CI 1.06 to 1.71, p=0.016) and arrhythmic mortality (1.61, 95% CI 1.12 to 2.30, p=0.009). The association held both in patients without heart failure (1.37, 95% CI 1.05 to 1.79, p=0.019) and with it (1.41, 95% CI 1.09 to 1.84, p=0.010), and there was no significant interaction with sex. The authors concluded that the findings call into question the widespread use of digoxin in atrial fibrillation. The standard objection is confounding by indication — digoxin tends to be given to patients who are sicker — and the authors addressed it by adjustment rather than by randomisation, which is not the same thing. What can be said with confidence is that there is no randomised evidence of a mortality benefit for digoxin in atrial fibrillation, that the observational evidence points the other way, and that no adequately powered randomised trial has settled it.
Written into the record, not signed off as a reviewed claim
The narrowest useful window of any common cardiac drug
In plain words
Below about 0.5 the drug does little; above about 2 it becomes dangerous without becoming more effective. Age, weight, kidney function and salt balance all move where a given dose lands inside that window.
What was measured
Serum concentration thresholds for diminished efficacy and for toxicity, and the enumerated predisposing factors, from the label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label states that serum digoxin levels below 0.5 ng/mL have been associated with diminished efficacy and levels above 2 ng/mL with increased toxicity without increased benefit — a fourfold window in a drug dosed in micrograms and cleared renally. Toxicity presents as nausea, vomiting, visual disturbance and cardiac arrhythmias, and advanced age, low body weight, impaired renal function and electrolyte abnormalities all predispose to it. The drug is contraindicated in ventricular fibrillation. It is specifically dangerous in Wolff-Parkinson-White syndrome with atrial fibrillation, where slowing atrioventricular conduction more than accessory-pathway conduction raises the risk of a rapid ventricular response and ventricular fibrillation. It can cause severe sinus bradycardia or sinoatrial block in pre-existing sinus node disease and advanced heart block in pre-existing incomplete AV block. It is not recommended in acute myocardial infarction and should be avoided in myocarditis, and it carries a risk of ventricular arrhythmias during electrical cardioversion. The mechanism explains the fragility: the binding site on the sodium pump is one where extracellular potassium competes, so a fall in potassium increases effective drug action at an unchanged blood level.
Source
LANOXIN (digoxin) United States prescribing information, sections 2, 4, 5.1 to 5.6 and 12.1 (NDA 020405)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
How many documents were read
44 documents were read for this substance.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
73K4184T59
CAS registry number
20830-75-5
PubChem compound
2724385
RxNorm concept
3407
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What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
20 approved applications cover products containing this substance. The earliest was NDA009330, approved 19541116 to AZURITY.
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7 questions this page could not answer
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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 drug in continuous use since 1785 whose first placebo-controlled mortality trial, in 1997, randomised 6,800 patients and found deaths of 34.8% against 35.1% (RR 0.99, 95% CI 0.91 to 1.07, p=0.80) while heart-failure hospitalisations fell from 34.7% to 26.8% (p<0.001) — a result its own FDA label now states in the indication itself, in the phrase "while having no effect on mortality".
Recorded evidence blocks (10)
Q2
On the Digoxin label: indicated for what?
"Digoxin Tablets are a cardiac glycoside indicated for: Treatment of mild to moderate heart failure in adults. ( 1.1 ) Increasing myocardial contractility in pediatric patients with heart failure.": indications and usage on Digoxin's label. DailyMed label · 5886e233-b2da-4acb-be05-9bf40fb8e7f4 · 2026-07-08
Q3
190 registered trials of Digoxin — at which phases?
Registered studies posting no result
155 of 190
190 registered studies of Digoxin: 143 phase1, 17 phase2, 10 phase4, 9 na, 9 phase3, 3 early phase1, 3 na or unstated. CLINICALTRIALS_SNAPSHOT · 2026-09-01
1.5 to 2 days; In healthy volunteers with normal renal function, digoxin has a half-life of 1.5 to 2 days.
bioavailabilitypharmacokinetics
60 to 80 %; Absorption of digoxin from Digoxin Tablets has been demonstrated to be 60 to 80% complete compared to an identical intravenous dose of digoxin (absolute bioavailability).
metabolismpharmacokinetics
Metabolism Only a small percentage (13%) of a dose of digoxin is metabolized in healthy volunteers.
recorded 2026-07-08 · last checked 2026-09-04
Q7
Which running trial of Digoxin could settle lifespan?
NCT06701812 measures Progression Free Survival at 4 months (PFS4), reading out 2027-02.
1 open trial; n 23; "Digoxin Medulloblastoma Study"
Show the evidence
TrialNCT06701812
"Digoxin Medulloblastoma Study"; n 23; "Progression Free Survival at 4 months (PFS4)"; 2027-02
Q8
Which 97 trials of Digoxin posted no result?
Posted no result
97 of 97 completed trials
Registrations
NCT00000556, NCT02262520, NCT01514812, NCT01518166, NCT00712465 and NCT00723424, and 91 more
Completion dates
oldest 2002-09; newest 2024-06-28
Show the evidence
Trial
NCT00000556
2002-09
NCT02262520
2006-03
NCT01514812
2006-04
NCT01518166
2007-04
NCT00712465
2008-11
NCT00723424
2008-12
14 further recorded trials
NCT01663961
2008-12
NCT00860223
2009-04
NCT00831506
2009-05
NCT00650910
2009-07-10
NCT00904176
2009-08
NCT01714206
2009-09
NCT01056874
2010-04
NCT01103622
2010-12
NCT01288742
2011-05
NCT01355354
2011-09
NCT01357811
2011-11
NCT01477411
2012-01
NCT01699776
2012-02
NCT01519128
2012-04
Q9
At the median, Digoxin's trials enrolled 30 people — anything larger?
Median enrolment
30
Largest enrolment
982
Registered trials counted
188
Q10
What do 5307 spontaneous reports say about Digoxin — 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.
Digoxin appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 5307 reaction mentions were counted: bradycardia 977; toxicity to various agents 836; nausea 553; dizziness 502. FAERS via Open Targets · CHEMBL1751 · 2026-06-24
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · 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
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