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Evidence: HighPeptideFDA ApprovedVasoconstrictor peptideFDA-approved · GiaprezaSeptic and distributive shock

Angiotensin II

The body's own blood-pressure hormone, given by intravenous infusion when shock does not respond to standard vasopressors

Angiotensin II is the eight-amino-acid hormone at the end of the renin-angiotensin system, and one of the strongest vessel constrictors the body makes. Synthetic angiotensin II is approved as Giapreza for adults in septic or other distributive shock. In its phase 3 trial it raised blood pressure in seven of ten patients; it did not significantly change survival.

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Overview

What is it?

Shock is blood pressure too low to keep organs supplied. In distributive shock, sepsis being the commonest cause, vessels dilate, and doctors raise pressure with noradrenaline and vasopressin. When those fail at high doses, mortality is high. Angiotensin II works through a third pathway, its own receptor on vessel walls, so it can add pressure when the other two are exhausted. Its plasma half-life is under a minute, so it runs as a continuous infusion.

The phase 3 trial, ATHOS-3, enrolled 321 patients still in shock on more than 0.2 µg/kg/min of noradrenaline or its equivalent. Mean arterial pressure responded at three hours in 69.9% on angiotensin II against 23.4% on placebo, and cardiovascular organ-failure scores improved more. Death by day 28 was 46% against 54%, a difference that was not statistically significant. Its 20-patient pilot showed it sharply cut the noradrenaline dose needed, with hypertension the commonest side effect.

Later analyses suggest who benefits. In ATHOS-3, patients whose pressure rose strongly at low doses had about half the mortality hazard of those who did not, and in a cohort of bacteraemic shock a quick fall in noradrenaline needs within three hours predicted survival. Post hoc, patients with severe kidney injury seemed to benefit most, and those already on ACE inhibitors or angiotensin receptor blockers responded differently; in kidney transplant patients, though, prior blockers did not blunt it.

Outside its pivotal trial, the evidence is mostly observational. Across about 3,000 reported patients, mortality has not differed from controls and thrombotic events were not increased; one large propensity-weighted cohort found lower 30-day mortality when it was added. Renin falls once it starts, and noradrenaline and vasopressin doses come down. Small paediatric series report responses, off label.

The label starts the infusion at 20 ng/kg/min and titrates every five minutes by up to 15, with a ceiling of 80 in the first three hours and 40 afterwards; doses as low as 1.25 ng/kg/min may be used. It is diluted in saline, and the label warns of thrombosis, so prophylaxis is advised.

69.9% vs 23.4%
Blood-pressure response at 3 h
ATHOS-3, 321 patients
20 → ≤80
ng/kg/min, first 3 hours
Giapreza label 2.2
<1 min
Plasma half-life
Label 12.3
Science

Mechanism of Action

Angiotensin II is the body's own vasoconstrictor peptide, given intravenously to raise blood pressure through the AT1 receptor when catecholamines and vasopressin fall short.

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AT1 receptor

Constricts vessels and releases aldosterone through the angiotensin type 1 receptor.

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A third vasopressor pathway

Works independently of adrenergic and vasopressin receptors, lowering their doses.

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Seconds-long

Plasma half-life under 1 minute; continuous infusion, no kidney or liver dose adjustment (label 12.3).

Evidence

Published Research

These are the trials that describe angiotensin II as a drug, read from their PubMed abstracts: the phase 3, its pilot and an analysis of patients on blood-pressure medicines.

Human2017

ATHOS-3, the phase 3

321 patients in vasodilatory shock on high-dose vasopressors received angiotensin II or placebo. 69.9% against 23.4% met the blood-pressure target at three hours; cardiovascular SOFA improved more (-1.75 vs -1.28); 28-day deaths were 46% against 54% (P=0.12).

PMID: 28528561
Human2014

The ATHOS pilot

20 patients with distributive shock received angiotensin II from 20 ng/kg/min or placebo for six hours. The hour-one noradrenaline dose was 7.4 against 27.6 µg/min; hypertension affected 20% on the drug; 30-day mortality was similar.

PMID: 25286986
Human2024

Patients on ACE inhibitors or ARBs

In a post hoc analysis of ATHOS-3's 321 patients, those exposed to neither drug gained 9.1 mmHg of mean arterial pressure at one hour on angiotensin II against placebo, and the response differed in the 29 on ACE inhibitors and 22 on receptor blockers.

PMID: 38637829
Human2025

ATHOS-3 patients with kidney injury

In a post hoc analysis of 203 ATHOS-3 patients with kidney injury, 28-day mortality was 53% against 63% on placebo (not significant); in stage 3 injury, 48% against 67%, a subgroup result.

PMID: 39671552
Human2025

An early response index

In ATHOS-3, 60% of patients on angiotensin II had a strong early pressure response per unit dose; each unit increase in this index was linked to a 16% lower hazard of death, and responders had about half the mortality hazard of resistant patients.

PMID: 39972379
Human2026

Response predicts outcome in bacteraemic shock

In 320 patients with septic shock from bloodstream infection, each 10% fall in noradrenaline-equivalent dose within 3 hours of starting angiotensin II was associated with lower 30-day mortality (adjusted odds ratio 0.83).

PMID: 42594819
Human2025

Multicentre propensity-weighted cohort

In a large multicentre cohort with 56.4% overall 30-day mortality, adding angiotensin II to conventional vasopressors was associated with lower mortality after weighting (odds ratio 0.74). It is observational.

PMID: 40699461
Human2025

Renin and vasopressor sparing

In 42 patients with distributive shock, mostly septic, noradrenaline and vasopressin doses fell after angiotensin II was started, and renin roughly halved; renin was lower in survivors.

PMID: 41046206
Human2025

Children in intensive care

In 14 critically ill children given 2.5 to 80 ng/kg/min for a median 32 hours, 71% responded with less vasopressor need or higher pressure; responders were older, and one child had peripheral ischaemia. Paediatric use is off label.

PMID: 41112332
Human2025

Kidney transplant patients on ARBs

In 65 kidney transplant recipients with perioperative low blood pressure, prior angiotensin receptor blocker use did not reduce the effect of angiotensin II.

PMID: 40564161
Review2025

About 3,000 patients reviewed

A systematic review of 59 studies covering 2,918 critically ill patients found no mortality difference in comparative studies and no increase in thrombotic or other adverse events.

PMID: 39800604
Dosing

Dosing Data

Giapreza is a continuous intravenous infusion in intensive care, started at 20 ng/kg/min and titrated every 5 minutes.

Intensive-care vasopressor; the label warns of thrombo-embolic events, and prophylaxis is advised.
ProtocolDoseFrequencyDurationRoute
Label: septic or other distributive shock, adults, start and first 3 hours Approved labelGiapreza (angiotensin II) injection US prescribing information (DailyMed set c265d69a, effective July 22, 2026)20 ng/kg/min, titrated by up to 15 every 5 minutes; max 80 ng/kg/minContinuous infusionFirst 3 hoursIntravenous
Label: maintenance Approved labelGiapreza (angiotensin II) injection US prescribing information (DailyMed set c265d69a, effective July 22, 2026)Up to 40 ng/kg/min (as low as 1.25)Continuous infusionWeaned as pressure allowsIntravenous

Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.

Nanograms per kilogram per minute
Angiotensin II is run by infusion pump in ng/kg/min in intensive care; there is nothing to prepare outside hospital.
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Safety

Side Effects & Contraindications

Reported Side Effects

From the Giapreza label and the trials above.

● Hypertension, from the drug doing its job too well, in 20% of the pilot
● Serious adverse events were common in both arms of ATHOS-3, 60.7% against 67.1%
● Given only by continuous infusion in intensive care
● Dose ceilings set by the label

Contraindications & Cautions

A hospital drug for shock.

● Use outside intensive care monitoring
● Known hypersensitivity to the product
● Tested athletes — see the Sport (WADA) row below
Questions

Frequently Asked Questions

?What is angiotensin II?

An eight-amino-acid hormone that constricts blood vessels and raises blood pressure. Synthetic angiotensin II is sold as Giapreza.

?When is it used?

In adults with septic or other distributive shock whose blood pressure stays low despite standard vasopressors.

?Does it save lives?

In ATHOS-3 it raised blood pressure in 69.9% against 23.4%, but the drop in 28-day deaths, 46% against 54%, was not significant.

?How is it dosed?

By intravenous infusion from 20 ng/kg/min, titrated to no more than 80 in the first three hours and 40 afterwards.

?Why is clot prevention needed?

The Giapreza label warns of venous and arterial thrombotic events in patients receiving it and tells clinicians to use venous thromboembolism prophylaxis at the same time.

Bibliography

References

  1. [fda-pi] Giapreza (angiotensin II) injection Prescribing Information, sections 1 and 2 (DailyMed version 18, effective July 22, 2026; read September 30, 2026).
  2. [pubmed] Khanna A, et al. "Angiotensin II for the Treatment of Vasodilatory Shock." N Engl J Med, 2017;377(5):419-430. PMID: 28528561.
  3. [pubmed] Chawla LS, et al. "Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study." Crit Care, 2014;18(5):534. PMID: 25286986.
  4. [pubmed] Leisman DE, et al. "ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock." Crit Care, 2024;28(1):130. PMID: 38637829.
  5. [fda-pi] Giapreza® (angiotensin II) Prescribing Information. La Jolla Pharmaceutical Company / Innoviva Specialty Therapeutics. Initial US approval December 21, 2017.
  6. [other] US FDA, Drugs@FDA (openFDA): GIAPREZA, NDA 209360, La Jolla Pharmaceutical, prescription. Read September 30, 2026.
  7. [pubmed] Chaba A, et al. "ANGIOTENSIN II FOR CATECHOLAMINE-RESISTANT VASODILATORY SHOCK IN PATIENTS WITH ACUTE KIDNEY INJURY: A POST HOC ANALYSIS OF THE ATHOS-3 TRIAL." Shock, 2025;63(1):88-93. PMID: 39671552.
  8. [pubmed] Kotani Y, et al. "The Efficacy and Safety of Angiotensin II for Treatment of Vasoplegia in Critically Ill Patients: A Systematic Review." J Cardiothorac Vasc Anesth, 2025;39(3):653-665. PMID: 39800604.
  9. [pubmed] Leisman DE, et al. "An index of the initial blood pressure response to angiotensin II treatment and its association with clinical outcomes in vasodilatory shock." Crit Care, 2025;29(1):81. PMID: 39972379.
  10. [pubmed] Khattar G, et al. "Early hemodynamic response to angiotensin II defines a prognostic phenotype in bloodstream infection-associated septic shock." J Crit Care, 2026;97:155708. PMID: 42594819.
  11. [pubmed] Busse LW, et al. "Angiotensin II, conventional vasopressor therapy, and mortality in shock: a large, multicenter, propensity score-weighted analysis." Ann Intensive Care, 2025;15(1):104. PMID: 40699461.
  12. [pubmed] Möller Petrun A, et al. "Real-world Experience of Angiotensin II and Renin Usage in Patients With Distributive Shock:A Single-center Descriptive Study." J Cardiothorac Vasc Anesth, 2025;39(12):3359-3367. PMID: 41046206.
  13. [pubmed] Dotolo N, et al. "Continuous Hemodynamic Response to Angiotensin II in Critically Ill Pediatric Patients: A Single Center Cohort Study." J Pediatr Pharmacol Ther, 2025;30(5):593-600. PMID: 41112332.
  14. [pubmed] Pettit N, et al. "Angiotensin Receptor Blockade Does Not Decrease Synthetic Angiotensin II (Giapreza(®)) Effectiveness in Perioperative Hypotension Surrounding Kidney Transplant." Biomedicines, 2025;13(6). PMID: 40564161.
  15. [fda-pi] Giapreza (angiotensin II) injection US prescribing information (DailyMed set c265d69a, effective July 22, 2026), section 2; read through openFDA October 6, 2026.

Sources & Citations

Studies were read from their PubMed abstracts; the Giapreza label from DailyMed (set c265d69a, effective July 22, 2026) through openFDA, read October 6, 2026.

Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.

Last reviewed: 2026-09-30