This page shows what was measured, who it was measured in, and what that does not settle.
What Isosorbide mononitrate does in the body
Preventing chest pain from narrowed heart arteries.
The drug releases nitric oxide, the same signalling molecule the lining of your blood vessels makes to tell them to relax. Nitric oxide switches on an enzyme inside vessel muscle that produces a messenger called cyclic GMP, and that messenger makes the muscle let go. Veins respond most, so blood pools in them and less returns to the heart; the heart therefore has less to pump each beat and needs less oxygen. That is what prevents the chest pain. The unusual part is that the effect fades if the drug never leaves the body, so the treatment is deliberately arranged to include a long stretch each day with none of it present.
What happened in people
Continuous treatment lost its chest-pain benefit within a day, and raising the dose did not restore it.
✓ 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
It did not clearly reduce deaths after a heart attack.
Where it acts
Venous capacitance vessels above all, then arterioles and the epicardial coronary arteries — the soluble guanylate cyclase inside their smooth muscle
Kind of result
Symptoms and quality of life
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · LX1OH63030 · read 2026-08-29
Its recorded molecular formula is C6H9NO6, weighing 191.14.
US prescribing information · f871dfa7-219f-4704-8e4d-215caeb7408d · read 2026-08-30
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 138 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.
Five-week all-cause mortality after suspected acute myocardial infarction, oral controlled-release mononitrate against matching placebo
2,129 (7.34%) against 2,190 (7.54%) deaths — no significant reduction overall or in any subgroup examined, and no later survival advantage
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. The only significant side effect was an increase of 15 per 1,000 in hypotension. Fewer deaths occurred on days 0 to 1 on active treatment, which the investigators read as reassuring about early nitrate safety.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Immediate-release tablet and extended-release tablet, taken orally
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononi… · a recorded source, not a stored snapshot
NEAT-HFpEF: nitrate effect on activity tolerance in heart failure with preserved ejection fraction (NCT02053493) · a recorded source, not a stored snapshot
Isosorbide mononitrate tablets United States prescribing information — Indications, Contraindications, Warnings, Clinical Pharmacology and Adverse Reactions … · a recorded source, not a stored snapshot
Daily activity level, as average daily accelerometer units during the highest-dose phase
-381 accelerometer units (95% CI -780 to 17), p=0.06 at the highest dose; hours of activity per day -0.30 (95% CI -0.55 to -0.05), p=0.02; across all doses -439 units (95% CI -792 to -86), p=0.02
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. The direction was against the drug. Activity fell progressively with increasing nitrate dose and not with increasing placebo dose, and there were no differences in six-minute walk, quality of life or NT-proBNP.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Immediate-release tablet and extended-release tablet, taken orally
Interval reported. 95% CI -780 to 17), p=0
Written into the record, not signed off as a reviewed claim.
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononi… · a recorded source, not a stored snapshot
NEAT-HFpEF: nitrate effect on activity tolerance in heart failure with preserved ejection fraction (NCT02053493) · a recorded source, not a stored snapshot
Isosorbide mononitrate tablets United States prescribing information — Indications, Contraindications, Warnings, Clinical Pharmacology and Adverse Reactions … · a recorded source, not a stored snapshot
Exercise tolerance in chronic stable angina
✓ The study showed what it set out to show
Who was studied
Six placebo-controlled antianginal studies in the registration programme
Antianginal efficacy demonstrated on exercise tolerance, beginning one hour after the first dose; the label states that duration of activity beyond fourteen hours has not been studied
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. Headache was dose-related, at 6% on placebo against 35% at the highest strength studied, with 5% of that group discontinuing. The endpoint is exercise time, not events.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Immediate-release tablet and extended-release tablet, taken orally
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononi… · a recorded source, not a stored snapshot
NEAT-HFpEF: nitrate effect on activity tolerance in heart failure with preserved ejection fraction (NCT02053493) · a recorded source, not a stored snapshot
Isosorbide mononitrate tablets United States prescribing information — Indications, Contraindications, Warnings, Clinical Pharmacology and Adverse Reactions … · a recorded source, not a stored snapshot
What we know
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.
Start
Isosorbide mononitrate
What a person takes: Immediate-release tablet and extended-release tablet, taken orally.
The measurement behind this step
The immediate-release and extended-release forms exist to solve the same problem from opposite directions: both are arranged so that the drug is absent from the body for a long stretch of each day, because continuous presence abolishes the effect. Bioavailability is near-complete because, unlike the dinitrate, the mononitrate is not removed on first pass, and the label states no adjustment is needed for age or for hepatic or renal impairment.
Getting in
Swallowed, and almost none of it is lost
Unlike its parent drug, this one is not destroyed on its first pass through the liver, so nearly all of what is swallowed reaches the circulation. Liver or kidney problems do not change that.
──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
Isosorbide mononitrate is the major active metabolite of isosorbide dinitrate and undergoes essentially no first-pass metabolism, giving near-complete bioavailability with low variability. The label states that dosage adjustments are not necessary for elderly patients or for altered hepatic or renal function.
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononi… · a recorded source, not a stored snapshot
NEAT-HFpEF: nitrate effect on activity tolerance in heart failure with preserved ejection fraction (NCT02053493) · a recorded source, not a stored snapshot
Reaching the cell
Vessel muscle has to activate it first
The tablet itself does nothing to a blood vessel. Enzymes inside the vessel wall have to break it down before nitric oxide is released.
╌╌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
Organic nitrates are prodrugs requiring enzymatic bioactivation within vascular smooth muscle to liberate nitric oxide. This is why decomposition rate in buffer says nothing useful about potency, and why the tolerance phenomenon is a property of the activating machinery rather than of the molecule.
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononi… · a recorded source, not a stored snapshot
NEAT-HFpEF: nitrate effect on activity tolerance in heart failure with preserved ejection fraction (NCT02053493) · a recorded source, not a stored snapshot
The change it makes
Nitric oxide switches on the relaxing enzyme
Nitric oxide binds an enzyme inside the muscle cell that makes a messenger called cyclic GMP. That messenger tells the muscle to let go.
╌╌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
Nitric oxide binds the haem group of soluble guanylate cyclase, raising cyclic GMP, which activates protein kinase G and lowers intracellular calcium. This is the identical end point that phosphodiesterase type 5 inhibitors reach by blocking cyclic GMP breakdown, which is why the two are absolutely contraindicated together.
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononi… · a recorded source, not a stored snapshot
NEAT-HFpEF: nitrate effect on activity tolerance in heart failure with preserved ejection fraction (NCT02053493) · a recorded source, not a stored snapshot
What that does for a person
Veins widen most, so the heart has less to pump
Blood pools in the widened veins and less returns to the heart. With less to move each beat, the heart needs less oxygen, and the mismatch that caused the pain narrows.
╌╌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
Venodilatation predominates: pooling reduces venous return, left ventricular end-diastolic pressure and pulmonary capillary wedge pressure. Arteriolar relaxation reduces systemic vascular resistance and arterial pressure, and coronary arteries dilate as well. The label states the relative importance of the three remains undefined.
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononi… · a recorded source, not a stored snapshot
NEAT-HFpEF: nitrate effect on activity tolerance in heart failure with preserved ejection fraction (NCT02053493) · a recorded source, not a stored snapshot
What that does for a person
Keep it there and it stops working
If the drug is present around the clock, the effect fades within a day and raising the dose does not bring it back. Only removing it for several hours restores it.
╌╌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 records that in the large majority of well-controlled exercise-testing trials, continuously delivered nitrates were indistinguishable from placebo after 24 hours or less, that dose escalation far beyond acutely effective doses has consistently failed to overcome tolerance, and that efficacy returns only after several hours of absence.
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononi… · a recorded source, not a stored snapshot
NEAT-HFpEF: nitrate effect on activity tolerance in heart failure with preserved ejection fraction (NCT02053493) · a recorded source, not a stored snapshot
What that does for a person
What the largest trial found
Fifty-eight thousand patients after a heart attack were given this drug or a dummy tablet. Deaths at five weeks were 7.34% and 7.54%. Nothing separated them, then or later.
──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
ISIS-4 found no significant reduction in five-week mortality overall or in any subgroup examined, including patients already on non-study nitrates, with no later survival advantage. In the same factorial trial captopril produced a significant 7% proportional mortality reduction, so the design could detect an effect of that magnitude.
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononi… · a recorded source, not a stored snapshot
NEAT-HFpEF: nitrate effect on activity tolerance in heart failure with preserved ejection fraction (NCT02053493) · a recorded source, not a stored snapshot
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 stable angina from coronary artery disease, to reduce how often the pain comes. Not people taking sildenafil, tadalafil, vardenafil or riociguat, where the combination can cause severe hypotension.
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: “Safety and effectiveness of isosorbide mononitrate in pediatric patients have not been established.”
US prescribing information · f871dfa7-219f-4704-8e4d-215caeb7408d · read 2026-08-30
On older people, the label states: “Clinical studies of isosorbide mononitrate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.”
US prescribing information · f871dfa7-219f-4704-8e4d-215caeb7408d · read 2026-08-30
On people who are pregnant, the label states: “Teratogenic Effects Pregnancy Category B Reproduction studies performed in rats and rabbits at doses of up to 540 and 810 mg/kg/day, respectively, have revealed no evidence of harm to the fetus due to isosorbide mononitrate.”
US prescribing information · f871dfa7-219f-4704-8e4d-215caeb7408d · read 2026-08-30
On people who are breastfeeding, the label states: “It is not known whether isosorbide mononitrate is excreted in human milk.”
US prescribing information · f871dfa7-219f-4704-8e4d-215caeb7408d · read 2026-08-30
Where the result stopped carrying
ISIS-4 found no mortality benefit in about 29,000 patients given the drug, and none in any subgroup
NEAT-HFpEF found less daily activity on the nitrate, with the effect growing as the dose rose
Continuous delivery abolishes the antianginal effect within a day, and dose escalation does not recover it
The label states that benefits in acute myocardial infarction and congestive heart failure have not been established and that the drug is not recommended there
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
Immediate-release tablet and extended-release tablet, taken orally
✎ 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
The immediate-release and extended-release forms exist to solve the same problem from opposite directions: both are arranged so that the drug is absent from the body for a long stretch of each day, because continuous presence abolishes the effect.
✎ 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: Bioavailability is near-complete because, unlike the dinitrate, the mononitrate is not removed on first pass, and the label states no adjustment is needed for age or for hepatic or renal impairment.
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
Absolutely contraindicated with phosphodiesterase type 5 inhibitors and with riociguat, where the combination can cause severe hypotension, syncope or myocardial ischaemia. Headache is dose-related and affected 35% at the highest studied strength. The label states that benefits in acute myocardial infarction or congestive heart failure have not been established, and that the drug is not recommended in those settings because its effects are difficult to terminate rapidly. Extremely rarely, ordinary doses of organic nitrates have caused methaemoglobinaemia.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononi… · a recorded source, not a stored snapshot
NEAT-HFpEF: nitrate effect on activity tolerance in heart failure with preserved ejection fraction (NCT02053493) · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Immediate-release tablet and extended-release tablet, taken orally
✎ 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: Bioavailability is near-complete because, unlike the dinitrate, the mononitrate is not removed on first pass, and the label states no adjustment is needed for age or for hepatic or renal impairment.
No source is stored against this line.
What is recorded as being sold
67 products list this as an active ingredient in the United States drug directory. 67 of them contain it and nothing else.
FDA National Drug Code directory · 71610-825 · read 2026-08-29
They are sold as powder, tablet and tablet, extended release, taken oral.
FDA National Drug Code directory · 71610-825 · read 2026-08-29
The regulator's established pharmacologic class for it is nitrate vasodilator [epc], nitrates [cs] and vasodilation [pe].
FDA National Drug Code directory · 71610-825 · read 2026-08-29
38 published labels name it as an active ingredient. 38 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 7443a5b6-6153-4227-870c-3c710f1f2174 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 7443a5b6-6153-4227-870c-3c710f1f2174 · read 2026-08-29
1845 marketed supplement labels list this ingredient, classed as vitamin.
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.
isosorbide mononitrate is oral at HOW SUPPLIED Isosorbide Mononitrate 20 mg Tablets, USP are white, round, scored and engraved "20" on one side and engraved "KU 107" on the other., recorded as fda label in effect 2019-11-01 in the United States.
US prescribing information · f871dfa7-219f-4704-8e4d-215caeb7408d · read 2026-08-30
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 Isosorbide mononitrate 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 nitrates reduce heart attacks or deaths — the largest trial ever run on the question found nothing
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 antianginal effect is primarily preload reduction, when the label says the relative importance of the three mechanisms remains undefined
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 nitrates improve exercise capacity in heart failure with preserved ejection fraction, which NEAT-HFpEF measured and found the opposite of
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 raising the dose restores an effect lost to tolerance, which the label says has consistently 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.
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 Isosorbide mononitrate 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.
ISIS-4: no survival benefit in 58,050 patients, and none in any subgroup
In plain words
One of the largest heart trials ever run gave oral mononitrate or a matching dummy tablet to fifty-eight thousand people after a suspected heart attack. Five-week deaths were 7.34% on the drug and 7.54% on placebo. There was no benefit in any group examined and none later either.
What was measured
Five-week all-cause mortality after suspected acute myocardial infarction
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
ISIS-4 randomised 58,050 patients entering 1,086 hospitals within 24 hours of suspected acute myocardial infarction, median 8 hours, in a two-by-two-by-two factorial design. One comparison was one month of oral controlled-release mononitrate against matching placebo, with about 29,000 patients per arm. There was no significant reduction in five-week mortality either overall — 2,129 (7.34%) mononitrate deaths against 2,190 (7.54%) placebo — or in any subgroup examined, including those already receiving non-study intravenous or oral nitrates at entry. Further follow-up showed no later survival advantage. The only significant side effect was an increase of 15 per 1,000 in hypotension. Patients allocated active treatment had somewhat fewer deaths on days 0 to 1, which the investigators describe as reassuring about the safety of early nitrate use. In the same trial, captopril produced a significant 7% proportional reduction in five-week mortality, so the trial was capable of detecting an effect of that size and did not detect one here.
Source
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group, Lancet 1995;345:669-685
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
NEAT-HFpEF: patients given the nitrate moved less, not more
In plain words
Nitrates are widely prescribed to help people with stiff-heart failure do more. A trial fitted 110 such patients with activity monitors and gave them the drug or placebo in turn. On the drug they were less active, and the more they took, the less they moved.
What was measured
Daily activity in accelerometer units and hours of activity per day, nitrate against placebo in crossover
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
NEAT-HFpEF was a multicentre, double-blind crossover study in 110 patients with heart failure and preserved ejection fraction, randomised to six weeks of dose-escalating isosorbide mononitrate or placebo and then crossed over. The primary endpoint was daily activity level as average daily accelerometer units during the highest-dose phase. At that dose there was a non-significant trend toward lower activity on the nitrate (-381 accelerometer units, 95% CI -780 to 17, p=0.06) and a significant decrease in hours of activity per day (-0.30 hours, 95% CI -0.55 to -0.05, p=0.02). Across all dose regimens, activity on the nitrate was lower than on placebo (-439 units, 95% CI -792 to -86, p=0.02), and activity fell progressively and significantly with increasing nitrate dose but not with increasing placebo dose. There were no between-group differences in six-minute walk distance, quality-of-life scores or NT-proBNP. The published conclusion is that these patients were less active and did not have better quality of life or submaximal exercise capacity than those receiving placebo.
Written into the record, not signed off as a reviewed claim
The label states the drug stops working within a day of continuous use
In plain words
This is written into the prescribing information rather than buried in a journal. Trials that delivered nitrates continuously found them indistinguishable from a dummy tablet after 24 hours or less, and raising the dose did not fix it.
What was measured
Exercise-test antianginal efficacy after continuous nitrate exposure, from the controlled trials summarised in the label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Clinical Pharmacology section states that the strategy of maintaining plasma concentrations continuously above a minimally effective level, standard for most chronic drugs, is inappropriate for organic nitrates. It records that several well-controlled trials using exercise testing found active agents indistinguishable from placebo after 24 hours or less of continuous therapy, and that attempts to overcome tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours is antianginal efficacy restored. The approved regimen is therefore deliberately asymmetric, leaving a long stretch of each day with the drug absent. The label adds that tolerance still occurs to some extent even on that regimen, and that the duration of antianginal activity beyond fourteen hours has not been studied.
Source
Isosorbide mononitrate United States prescribing information, Clinical Pharmacology and Dosage and Administration sections
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
The mechanism is described in the label as undefined
In plain words
Nitrates widen veins, widen arteries and widen the coronary vessels. Which of those three actually stops the chest pain has not been settled, and the prescribing information says so.
What was measured
That the antianginal effect is primarily preload reduction — the most commonly taught account, which the label declines to endorse over the alternatives
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label describes dilatation of peripheral arteries and veins, especially veins, with venous pooling reducing venous return and therefore left ventricular end-diastolic pressure and pulmonary capillary wedge pressure; arteriolar relaxation reducing systemic vascular resistance and arterial pressure; and dilatation of the coronary arteries. It then states: the relative importance of preload reduction, afterload reduction and coronary dilatation remains undefined. This is unusually candid for a drug in use since the nineteenth century in its parent form, and it matters for the tolerance question, because a mechanism that has not been isolated is a mechanism whose loss cannot be measured directly either.
Source
Isosorbide mononitrate United States prescribing information, Clinical Pharmacology section
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
Two absolute contraindications built on the same second messenger
In plain words
Erectile dysfunction drugs and this drug both raise the same chemical signal in blood vessel walls, by different steps. Together they can drop blood pressure catastrophically.
What was measured
Not recorded
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The label contraindicates concomitant use with phosphodiesterase type 5 inhibitors — sildenafil, tadalafil, vardenafil — and with the soluble guanylate cyclase stimulator riociguat, stating that the combinations can cause severe hypotension, syncope or myocardial ischaemia. Nitrates raise cyclic GMP by donating nitric oxide to activate soluble guanylate cyclase; PDE5 inhibitors raise it by blocking its breakdown; riociguat raises it by stimulating the same cyclase directly. The label notes that the time course and dose dependence of the sildenafil interaction have not been studied, and that appropriate supportive care has not been studied either, suggesting it be treated as a nitrate overdose. Separately, the label states that benefits in acute myocardial infarction or congestive heart failure have not been established and that the drug is not recommended in those settings because its effects are difficult to terminate rapidly.
Source
Isosorbide mononitrate United States prescribing information, Contraindications and Warnings sections
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
Headache in a third of patients at the higher strength
In plain words
The headache is the drug working on the wrong blood vessels. It affected six percent of people on the dummy tablet and thirty-five percent at the higher strength, and it faded after the first few days.
What was measured
Headache incidence and discontinuation across six placebo-controlled studies
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Across six placebo-controlled studies, headache occurred in 6% of 160 placebo patients, 17% of 54 at the lowest strength, 13% of 52 at the intermediate strength and 35% of 159 at the highest studied strength, with 5% of that last group discontinuing for it. Headache was the cause of 2% of all dropouts from the controlled trial programme and decreased in incidence after the first few days of therapy. Other reactions above 1% were fatigue, dizziness and nausea. The label records that extremely rarely, ordinary doses of organic nitrates have caused methaemoglobinaemia.
Source
Isosorbide mononitrate United States prescribing information, Adverse Reactions section
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
38 documents were read for this substance.
RNAWiki source record
38 of them state the same halfLife, and they agree.
RNAWiki source record
29 of them state the same bioavailability, and they agree.
RNAWiki source record
9 of them state the same proteinBinding, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
LX1OH63030
RxNorm concept
311196
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Identity resolved
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no quarantine open
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Every public sentence names a source
The opening statement carries the origin: Reviewed first-read answer.
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Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
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Safety mode resolved
No register row and no identity class settled the question.
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Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
23 approved applications cover products containing this substance. The earliest was NDA019091, approved 19911230 to PROMIUS PHARMA.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A long-acting nitric oxide donor that widens veins and reduces the work of the heart, whose antianginal effect its own label says disappears within 24 hours of continuous exposure and cannot be recovered by raising the dose — and which, given to 29,000 patients after myocardial infarction in ISIS-4, produced five-week mortality of 7.34% against 7.54% on placebo.
Recorded evidence blocks (9)
Q1
On the Isosorbide mononitrate label: indicated for what?
"Isosorbide Mononitrate Tablets USP are indicated for the prevention and treatment of angina pectoris due to coronary artery disease. The onset of action of oral isosorbide mononitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.": indications and usage on Isosorbide mononitrate's label. DailyMed label · 55f240e1-3056-38cc-e063-6294a90a814e · 2026-07-06
Q2
29 registered trials of Isosorbide mononitrate — at which phases?
5 hours; The overall elimination half-life of isosorbide mononitrate is about 5 hours.
tmaxpharmacokinetics
30-60 minutes; Peak plasma concentrations usually occur in about 30-60 minutes.
bioavailabilitypharmacokinetics
100 %; The absolute bioavailability of isosorbide mononitrate from isosorbide mononitrate tablets is nearly 100%.
metabolismpharmacokinetics
In humans, isosorbide mononitrate is not subject to first pass metabolism in the liver.
recorded 2026-07-06 · last checked 2026-09-04
Q6
Which 13 trials of Isosorbide mononitrate posted no result?
Posted no result
13 of 13 completed trials
Registrations
NCT00450164, NCT02485340, NCT02712125, NCT02481323, NCT03407521 and NCT03255512, and 7 more
Completion dates
oldest 2004-06; newest 2024-06-30
Show the evidence
Trial
NCT00450164
2004-06
NCT02485340
2015-08
NCT02712125
2015-08
NCT02481323
2017-11-30
NCT03407521
2017-12-15
NCT03255512
2018-03-23
7 further recorded trials
NCT03557580
2018-05-18
NCT03665779
2019-05-01
NCT03799133
2019-12-28
NCT04217668
2020-03-12
NCT04312048
2020-11-30
NCT05800938
2022-12-06
NCT03544606
2024-06-30
Q7
At the median, Isosorbide mononitrate's trials enrolled 60 people — anything larger?
Median enrolment
60
Largest enrolment
3156
Registered trials counted
29
Q8
What do 855 spontaneous reports say about Isosorbide mononitrate — 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.
Isosorbide mononitrate appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 855 reaction mentions were counted: hypotension 234; dizziness 121; syncope 79; dyspnoea 76. FAERS via Open Targets · CHEMBL1311 · 2026-06-24
Show the evidence
hypotension
234
dizziness
121
syncope
79
dyspnoea
76
chest pain
73
acute kidney injury
64
4 more recorded rows
drug hypersensitivity
58
bradycardia
53
angina pectoris
50
orthostatic hypotension
47
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Isosorbide mononitrate's label not list?
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
✗ 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
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.