Peptide Graded

All peptides / Circulation

Angiotensin II

Vasopressor peptide

Also Giapreza, Angiotensin 2, Ang II, LJPC-501

Evidence
AStrong human evidence
FDA status
FDA approvedas of 2026-10-26
Route
Intravenous
Studies cited
1 human0 animal or cell

It is a hospital drug that raises blood pressure in people in shock. A trial of 344 patients showed it works for that, but it did not show that patients lived longer.

Sold for

Angiotensin II is an intensive-care drug, and discussion of it concerns whether it saves lives in septic shock when norepinephrine is not enough.

Studies say

A 344-patient randomized trial showed it raises blood pressure in shock patients who are not responding to other vasopressors, which earned approval, but it did not show that patients live longer.

Why grade A. Approval rests on ATHOS-3, a randomized, double-blind, placebo-controlled trial in 344 adults with vasodilatory shock that met its blood-pressure endpoint. That is one trial with a surrogate endpoint, but a regulator accepted it for approval and it is the use the drug is known for, which fits grade A as defined here; no survival benefit has been shown. 45

FDA. Synthetic human angiotensin II is FDA-approved and sold as Giapreza, approved in December 2017 as an intravenous infusion to raise blood pressure in adults with septic or other distributive shock. 24

Written from 5 cited sources. Last refreshed 2026-10-27. Not physician reviewed.

What this means for you

What people take it for
Very low blood pressure in shock
Can a US doctor prescribe it?
Yes, FDA approved for low blood pressure in septic or other types of shock.
Properly tested in people?
Yes, in a large controlled trial of 344 adults with shock.

Evidence checklist

  • Randomised controlled trial ATHOS-3, double-blind, placebo-controlledyes
  • Human study over 100 people ATHOS-3, 344 adults with shockyes
  • More than one research group One main trial from the makerno
  • Clinical outcomes, not surrogate markers Blood pressure target met; no survival gainno
  • Human safety data beyond case reports Clot and other events tracked in ATHOS-3yes

Drawn from the cited studies below. A dash means the sources give no information.

What it is

Angiotensin II is a peptide hormone with eight amino acids. The body makes it as part of the renin-angiotensin system. This chain of signals controls blood pressure and salt balance. The story starts in 1898, when kidney extracts were shown to raise blood pressure. In the late 1930s, two groups in Argentina and Indianapolis worked in parallel. They isolated the active substance and named it hypertensin and angiotonin. In 1958 they agreed on 'angiotensin'. 13

The drug Giapreza, from La Jolla Pharmaceutical, is a lab-made version of the human peptide. Nurses give it as a steady drip into a vein in intensive care. Doctors use it with standard vasopressors such as norepinephrine, not in place of them. 24

How it works

Angiotensin II binds the AT1 receptor on the smooth muscle of small arteries. The arteries narrow and blood pressure rises. It also tells the adrenal glands to release aldosterone, which makes the kidneys keep salt and water. It triggers release of vasopressin too. In distributive shock, the blood vessels are too wide and leaky. Angiotensin II gives a squeeze signal through a pathway that norepinephrine and vasopressin do not use. 14

What human research shows

ATHOS-3 appeared in the New England Journal of Medicine in 2017. It randomized 344 adults with vasodilatory shock to angiotensin II or placebo. All had low blood pressure despite high doses of standard vasopressors. At three hours, 69.9% of the angiotensin II group reached the target blood pressure. With placebo, 23.4% did. Doctors could lower the other vasopressor doses in the treated group. 5

By day 28, 46% of patients on angiotensin II had died, against 54% on placebo. That gap was not statistically significant. The trial was not built to detect a difference in deaths. No later randomized trial has shown a survival benefit. 5

StudyModelFinding
ATHOS-3, NEJM 2017Humans, n=344 adults with vasodilatory shock, randomized double-blind placebo-controlledBlood pressure response at 3 hours in 69.9% with angiotensin II versus 23.4% with placebo; 28-day mortality 46% versus 54%, not statistically significant. 5
FDA label, Giapreza 2017Regulatory review of ATHOS-3 safety dataThromboembolic events in 12.9% versus 5.1% with placebo led to a label recommendation for concurrent VTE prophylaxis. 4
History of the renin-angiotensin systemHistorical reviewAngiotensin was isolated independently in Buenos Aires and Indianapolis in the late 1930s and named by agreement in 1958. 3

Safety

In ATHOS-3, 12.9% of patients on angiotensin II had blood clot events, including deep vein thrombosis. On placebo, 5.1% did. So the FDA label advises clot prevention for veins during treatment. The drug group also had more low platelet counts, fast heart rate, delirium, acidosis, fungal infection and poor blood flow to the limbs. 45

The trial enrolled only patients in refractory shock who were monitored in intensive care. So nothing is known about the drug in other settings. It is not used outside hospitals. 4

Questions for your clinician

  • Does this drug improve survival in my situation, or only raise blood pressure?
  • How are clot risks managed while it is given?
  • Are there other vasopressors that have been compared directly with it?

Questions people ask

Is angiotensin II FDA-approved?

Yes. Giapreza was approved in December 2017 to raise blood pressure in adults with septic or other distributive shock. It is given only by drip into a vein in hospital. 24

Does Giapreza improve survival in septic shock?

Not as far as trials show. ATHOS-3 found no significant difference in 28-day deaths (46% versus 54%). It was designed to test blood pressure. No later trial has shown a survival benefit. 5

Why not just give more norepinephrine?

Patients in ATHOS-3 were already on high doses of standard vasopressors and still had low blood pressure. Angiotensin II works through a different receptor. So it adds a squeeze signal, and doctors could lower the other drugs. 45

What are the main risks?

Blood clots were the main warning sign. Clot events were about twice as common as with placebo in the approval trial. So doctors are advised to prevent clots during treatment. Poor blood flow to the limbs and delirium were also reported. 45

Citations

  1. StatPearls: Physiology, renin angiotensin system ncbi.nlm.nih.gov
  2. La Jolla Pharmaceutical: Giapreza product site giapreza.com
  3. Basso 2001, Hypertension: history of the discovery of the renin-angiotensin system pubmed.ncbi.nlm.nih.gov
  4. FDA: Giapreza (angiotensin II) prescribing information, 2017 accessdata.fda.gov
  5. Khanna 2017, NEJM: angiotensin II for the treatment of vasodilatory shock (ATHOS-3) doi.org

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