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Lexicon
Lexicon

Ramipril (Altace)

The ACE inhibitor with the broadest outcome evidence - and with the notorious dry cough.

3 min read 8 sources

To the sources
Large molecule model of glossy blue, light blue and white spheres floats above a white podium with a glowing rim in a bright lab, symbolic image for ramipril
Compound approved · since 1991

Summary

At a glance

Sources checked on 26 Oct 2026

Infarction, stroke, cardiac death (HOPE)
−22 %

9,297 high-risk people without heart failure, against placebo, mean of 5 years1

Mortality after infarction (AIRE)
−27 %

2,006 people with signs of heart failure after infarction, mean of 15 months3

Monthly decline in kidney function (REIN)
0.53 ml/min

versus 0.88 on placebo, with heavy protein in the urine4

Half-life (ramiprilat)
~15 hours

13 to 17 hours in the therapeutic range with daily dosing6

  • Ramipril is an ACE inhibitor. The liver converts it to ramiprilat, which slows the formation of angiotensin II. The vessels widen and aldosterone release falls.86
  • In HOPE infarction, stroke and cardiac death together fell by 22 percent in high-risk people without heart failure. After an infarction with heart failure mortality in AIRE was 27 percent lower.13
  • In kidney disease with heavy protein in the urine kidney function declined more slowly on ramipril (REIN). In MICRO-HOPE there was 24 percent less overt kidney damage in diabetes.42
  • Combined with a sartan, ramipril brought no added benefit in ONTARGET but more kidney problems. Dry cough is the best known side effect.56
  • According to ChEMBL ramipril has been approved since 1991. Everything here is the state of research, not a recommendation.8
Profile

Updated July 2026

How long does it stay in the body?

Share left after one dose, calculated with a half-life of ~15 hours

Half-life ~15 hours
After 30 hours: 25 %
Hour 15 · 50 %Hour 24, next dose · 33 %Hour 30 · 25 %Hour 45 · 12.5 %Hour 75 · 3.1 %

Simplified model without an absorption phase, half-life from the TPD lexicon. The lexicon gives 13 to 17 hours, we calculate with the middle.

Class
ACE inhibitor

prodrug, active as ramiprilat

Use
Oral

once daily

Half-life
13 to 17 hours

ramiprilat, effective

Best known side effect
Dry irritating cough in around 10 percent
Status
Clinically approved

standard agent

Contents 12 sections
  1. At a glance
  2. What is ramipril?
  3. How it works
  4. Use and dosing
  5. What the research shows
  6. Research status
  7. Side effects
  8. Storage
  9. Related compounds
  10. FAQ
  11. Glossary
  12. Sources

What is ramipril?

Ramipril is an ACE inhibitor. It blocks angiotensin-converting enzyme, which turns angiotensin I into angiotensin II. Angiotensin II is the body's strongest vasoconstrictor and additionally drives aldosterone release, meaning salt and water retention. Both fall away when the enzyme is blocked.

Ramipril itself is a prodrug and is converted in the liver into ramiprilat, which does the actual work. Beyond lowering blood pressure, this class has a well documented protective effect on kidney and heart that goes beyond the pressure effect.

This information is for research and educational purposes only. No medical advice.

Comparison

Different paths on blood pressure

Ramipril, sartans, spironolactone and amlodipine act at different points, as stated in the TPD lexicon. Tap a card to open its entry.

ACE inhibitor Ramipril (Altace) ACE
Sartan Telmisartan AT1 Sartan Losartan (Cozaar) AT1 Aldosterone antagonist Spironolactone (Aldactone) MR Calcium channel blocker Amlodipine (Norvasc) CACNA1C

Simplified: ACE inhibitors slow the formation of angiotensin II, sartans block its receptor, spironolactone blocks aldosterone, amlodipine the calcium channel of vessel muscles. 8

How it works

ACE has a second job. That is where the best known side effect comes from: it breaks down bradykinin. Block the enzyme and bradykinin accumulates. In the vessels that is welcome, because it widens them further. In the bronchi it causes a dry irritating cough in roughly one in ten. That cough does not go away.

The kidney effect works through widening of the efferent vessel in the glomerulus. Filtration pressure falls, the kidney is unloaded and protein excretion drops. That is exactly why the class is standard in proteinuric kidney disease, even though creatinine often rises slightly right after starting. A rise of up to about 30 percent is expected with ACE inhibitors and is not a reason to stop.

Where it acts

Where ramipril acted in studies

Tap a point or a card. Colour = ACE, grey = observed in studies.

  1. Blood vessels

    Less angiotensin II, vessels widen, less aldosterone6

    ACE
  2. Heart

    22 percent fewer infarctions, strokes and cardiac deaths (HOPE)1

    Observed in trials
  3. Kidney

    Slower decline in filtration rate with heavy protein in the urine (REIN)4

    Observed in trials
  4. Brain

    Stroke in 3.4 instead of 4.9 percent (HOPE)1

    Observed in trials
  5. Airways

    Dry cough, ACE otherwise also breaks down bradykinin6

    Observed in trials

Targets in the ChEMBL database8

Compound CHEMBL1168: one recorded mechanism, Inhibitor, direct binding.

Angiotensin-converting enzyme
Gene
ACE
UniProt
P12821
ChEMBL
CHEMBL1808
Action
Inhibitor, direct binding
Transparent light blue vessel with a grey, lumpy enzyme on the inner wall to which blue molecule models dock, next to it a bulge holding more molecules
Ramiprilat binds to angiotensin-converting enzyme. Symbolic image.

Use and dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts
White folding box with the TPD logo next to a blister of ten round white tablets, two loose tablets in front on a bright lab bench
Tablets in a blister. Symbolic image.

What the research shows

HOPE (NEJM 2000) is the trial that built the reputation of this substance. Over 9,000 patients at high cardiovascular risk but without heart failure received 10mg ramipril or placebo. The combined endpoint of heart attack, stroke and cardiovascular death fell by 22 percent. The blood pressure drop alone was too small to explain that, which suggests part of the benefit does not hang on pressure.

MICRO-HOPE (Lancet 2000) saw the same direction in the diabetes subgroup with less nephropathy on top. AIRE (Lancet 1993) showed 27 percent lower mortality after heart attack with heart failure. REIN (Lancet 1997) demonstrated the kidney protection directly: the decline in filtration slowed. Fewer patients reached end-stage renal failure.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

Fewer events against placebo123

Relative risk reduction of the primary outcome, values from the abstracts

HOPE1 Infarction, stroke, cardiac death, high risk
Ramipril -22%
MICRO-HOPE2 Same outcome, people with diabetes only
Ramipril -25%
AIRE3 Mortality after infarction with heart failure
Ramipril -27%

HOPE as relative risk 0.78, MICRO-HOPE and AIRE as stated in the abstract. Groups and outcomes differ, the bars cannot be read directly against each other.

Share with an event in about 5 years1

9,297 people aged 55 or older with vascular disease or diabetes plus a risk factor

Primary outcome1
Placebo 17.8%
Ramipril 14.0%
Myocardial infarction1
Placebo 12.3%
Ramipril 9.9%
Heart failure1
Placebo 11.6%
Ramipril 9.1%
Cardiac death1
Placebo 8.1%
Ramipril 6.1%
Stroke1
Placebo 4.9%
Ramipril 3.4%

Overall mortality was 10.4 instead of 12.2 percent. In MICRO-HOPE the benefit remained the same after adjusting for the small drop in blood pressure.

Decline in filtration rate per month4

Kidney disease without diabetes with at least 3 g protein in 24-hour urine

REIN, stratum 24 56 versus 61 evaluable people
Placebo 0.88 ml/min
Ramipril 0.53 ml/min

Doubling of creatinine or kidney failure affected 18 people on ramipril and 40 on placebo. Blood pressure was equally well controlled in both groups.

Same benefit, more problems together5

25,620 people with vascular disease or diabetes, median 56 months

Primary outcome5 Cardiac death, infarction, stroke, hospital for heart failure
Ramipril 16.5%
Telmisartan 16.7%
Ramipril plus telmisartan 16.3%
Renal dysfunction5
Ramipril 10.2%
Ramipril plus telmisartan 13.5%
Hypotensive symptoms5
Ramipril 1.7%
Telmisartan 2.6%
Ramipril plus telmisartan 4.8%

Telmisartan was equivalent to ramipril. The combination lowered blood pressure slightly more but brought no added benefit.

Lab shelf with stacks of clear petri dishes, in the middle a kidney and a heart made of clear glass
The large trials measured heart and kidney events. Symbolic image.

Research status

Where the research stands

Ramipril has been approved since 1991. On ClinicalTrials.gov 204 trials list ramipril among their interventions. HOPE, MICRO-HOPE, AIRE and REIN ran before the registry and are not listed there. Shown are large registered trials with ramipril. As of 26 Oct 2026. 7

  1. Preclinical Principle: inhibition of angiotensin-converting enzyme
  2. Phase 1 no registered trial
  3. Phase 2 no registered trial
  4. Phase 3 2 trials, 2 completed
  5. Approval since 1991
0 participants in phase 3 Approved: ChEMBL lists ramipril with phase 4 as the highest phase and first approval in 1991.8
Show all 3 phase 3 and 4 trials on a timelineHide timeline 3 completed 0 running 1 with results
Phase 3
Phase 4

Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026.

Side effects

  • Dry irritating cough: around 10 percent. Harmless, but it does not go away and it does not improve. If it appears, switching to a sartan such as losartan is the answer, since they work similarly without that effect.
  • Angioedema: rare but serious. Swelling of lips, tongue or throat needs immediate attention and means the definitive end of this substance class.
  • Raised potassium: especially combined with spironolactone or potassium supplements.
  • Dizziness on the first dose: hence starting low and taking it in the evening.
  • Creatinine rise: a rise of up to about 30 percent is expected. Clearly more than that needs checking.

Tolerability

Reasons for stopping in HOPE

How often a side effect led to stopping or pausing treatment in HOPE, over a mean of 5 years.

2 of 100 Placebo
7 of 100 Ramipril
Event PlaceboRamipril
Cough6 2%7%
Low blood pressure or dizziness6 2%2%
Angioedema6 0%0%

In a later one-year study increased cough occurred in almost 12 percent, about 4 percent stopped because of it. In ONTARGET cough was recorded in 4.2 percent on ramipril and 1.1 percent on telmisartan.65

Storage

Store dry, at room temperature and protected from light. Keep out of reach of children.

Three white tablet bottles on a bright shelf next to a folded light blue towel
Dry, at room temperature and away from light. Symbolic image.
Level · Ramipril (Altace)

How the level builds up

One dose per day: each dose adds to what is left of the previous one.

Lexicon: Oral, once daily
Peak 1.49×Trough 0.49×
Day 2 · 3. dose
1.44× of the first dose
Plateau
from Day 2

96 % of the plateau after dose 3

Peak
1.49×

of the first dose

Trough
0.49×

before the next dose

Simplified model, values relative to the first dose, no dosing information. Dashed: the first dose alone, green: the plateau.

Related

Related compounds

A different path: all in the TPD lexicon.

Ramipril (Altace)
Telmisartan Sartan, equivalent in ONTARGET, less cough Losartan (Cozaar) Sartan, works similarly without the bradykinin cough Spironolactone (Aldactone) Raises potassium like ramipril, together only with bloodwork Amlodipine (Norvasc) Different path, widens vessels via the calcium channel Rosuvastatin (Crestor) Different path, blood lipids instead of blood pressure (HOPE-3)

FAQ

Common questions about Ramipril (Altace)

Short answers, each backed by the sources below.

How does ramipril work?

Ramipril is a precursor. The liver splits it into ramiprilat, which according to the label acts about six times more strongly on the enzyme. It inhibits angiotensin-converting enzyme, so less angiotensin II is formed. The vessels widen and less aldosterone is released.68

Is ramipril approved?

Yes. ChEMBL lists ramipril as an approved compound with first approval in 1991. On ClinicalTrials.gov 204 trials list ramipril among their interventions (as of 26 October 2026). Everything here is the state of research, not a recommendation.87

What did the HOPE trial show?

9,297 high-risk people without heart failure received the highest study dose of 10 mg or placebo. Infarction, stroke or cardiac death affected 14.0 instead of 17.8 percent. In the diabetes group (MICRO-HOPE) blood pressure fell by only 2.4 over 1.0 mmHg, yet the benefit was 25 percent.12

Why the dry cough?

ACE also breaks down bradykinin. If the enzyme is inhibited, more bradykinin remains, which can trigger cough in the airways. According to the label almost 12 percent had increased cough in a one-year study. In HOPE cough was a reason to stop in 7 instead of 2 percent.6

Why not together with a sartan?

In ONTARGET more than 25,000 people received ramipril, telmisartan or both. The primary outcome was practically the same at 16.3 percent with the combination as at 16.5 percent with ramipril alone. Renal dysfunction, however, occurred in 13.5 instead of 10.2 percent, hypotensive symptoms in 4.8 instead of 1.7 percent.5

What does research show in the kidney?

In REIN, in kidney disease with heavy protein in the urine, filtration rate fell by 0.53 instead of 0.88 ml/min per month on ramipril. The advantage went beyond the drop in blood pressure. In MICRO-HOPE there was 24 percent less overt kidney damage in diabetes.42

What about potassium?

Because less aldosterone is released, potassium can rise slightly. According to the label about 4 percent had an abnormally high potassium value in a study lasting up to 56 weeks. Potassium-sparing drugs such as spironolactone add to this.6

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

ACE inhibitor
Drug class that inhibits angiotensin-converting enzyme and so lowers blood pressure.
Aldosterone
Adrenal hormone that retains salt and water in the body and excretes potassium.
Angioedema
Sudden swelling of skin and mucous membranes, for example of the lips, tongue or throat.
Angiotensin II
Body's own messenger that strongly narrows vessels and drives aldosterone release.
Bradykinin
Messenger that widens vessels. If it accumulates, it can trigger cough and rarely swelling.
Creatinine
Breakdown product from muscle in the blood. If it rises, the kidney filters less well.
Filtration rate (GFR)
How much blood the kidneys filter per minute. The most important measure of kidney function.
Nephropathy
Damage to the kidney, in diabetes often first seen as protein in the urine.
Ramiprilat
The active form into which the liver converts ramipril.
Sartan
Drug class that blocks the receptor of angiotensin II instead of slowing its formation.

Evidence

Sources

Show all 8 sourcesHide sources 5 Studies1 Trial registry2 Database checked 26 Oct 2026

Studies

  1. HOPE: ramipril at high cardiovascular risk

    HOPE Study Investigators (Yusuf et al.), New England Journal of Medicine, 2000

    DOI 10.1056/NEJM200001203420301 PMID 10639539
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  2. MICRO-HOPE: ramipril in diabetes

    Heart Outcomes Prevention Evaluation Study Investigators, The Lancet, 2000

    DOI 10.1016/S0140-6736(99)12323-7 PMID 10675071
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. AIRE: ramipril after infarction with heart failure

    AIRE Study Investigators, The Lancet, 1993

    DOI 10.1016/0140-6736(93)92693-N PMID 8104270
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  4. REIN: ramipril in kidney disease with protein in the urine

    GISEN Group, The Lancet, 1997

    DOI 10.1016/S0140-6736(96)11445-8 PMID 9217756
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  5. ONTARGET: ramipril, telmisartan or both

    ONTARGET Investigators (Yusuf et al.), New England Journal of Medicine, 2008

    DOI 10.1056/NEJMoa0801317 PMID 18378520 NCT00153101
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed

Trial registry

  1. Trials on ramipril on ClinicalTrials.gov

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. US prescribing information for ramipril

    DailyMed, U.S. National Library of Medicine (Stand 05.06.2026)

    Checked 26 Oct 2026 via DailyMed, openFDA
  2. Mechanism and approval in ChEMBL

    ChEMBL, EMBL-EBI (CHEMBL1168)

    Checked 26 Oct 2026 via ChEMBL