Angiotensin II
Angiotensin II (Giapreza, LJPC-501)
Written by Aaron CuhaReviewed Sep 2026
Also known as: Ang II, Giapreza, LJPC-501, Angiotensin II acetate
The body's main blood-pressure hormone, approved as an intravenous drug for shock that no longer responds to standard vasopressors. Its pivotal trial in 344 people met a blood-pressure endpoint; death by day 28 was 46 percent on angiotensin II and 54 percent on placebo, a difference that was not statistically significant.
Overview
Angiotensin II is an 8 amino acid peptide, sequence DRVYIHPF, cut out of angiotensinogen by renin and then by angiotensin-converting enzyme. It is the business end of the renin-angiotensin system: it constricts blood vessels, drives aldosterone release and promotes sodium retention. Almost everything most readers know about it comes from drugs that block it, since ACE inhibitors and angiotensin receptor blockers are among the most prescribed medicines in the world.
Since 2017 it has also been a drug in its own right. In ATHOS-3, 344 adults with vasodilatory shock already receiving more than 0.2 micrograms per kilogram per minute of norepinephrine or the equivalent were randomised to an angiotensin II infusion or placebo, and 321 were analysed. The primary endpoint, a mean arterial pressure response at hour 3, was reached by 69.9 percent on angiotensin II and 23.4 percent on placebo. Death by day 28 occurred in 46 percent versus 54 percent, hazard ratio 0.78, 95 percent confidence interval 0.57 to 1.07. The trial was funded by La Jolla Pharmaceutical Company, which sells the drug.
Regulatory position, checked on 11 September 2026 through openFDA: GIAPREZA, application NDA 209360, La Jolla Pharma, original approval 21 December 2017. Two product presentations are listed Prescription and one is listed Discontinued. A generic angiotensin II acetate injection from Gland, ANDA 216966, was approved on 3 June 2025.
This is an intensive care drug with a plasma half-life of under a minute, given by infusion through a central line to people on multiple vasopressors. It has no wellness, performance or longevity use, and there is no oral or subcutaneous product.
Mechanism of action
In humans, angiotensin II binds the AT1 receptor on vascular smooth muscle to cause vasoconstriction, and on the adrenal cortex to release aldosterone, which retains sodium and water. The AT2 receptor generally opposes those effects. In vasodilatory shock the catecholamine and vasopressin pathways are saturated or failing, and the rationale for giving angiotensin II is that it raises blood pressure through a third, independent receptor system. The counter-regulatory arm of the same peptide family, angiotensin-(1-7) acting at the Mas receptor, is described on its own page.
Human evidence
One randomised placebo-controlled phase 3 trial in 344 critically ill adults, several post-hoc analyses of that same trial, and small observational cohorts from hospitals that adopted the drug. Everything published is in intensive care.
- ATHOS-3 (2017): 344 randomised, 321 analysed. Blood pressure response at hour 3 in 69.9 percent versus 23.4 percent on placebo. Cardiovascular SOFA score improved more on angiotensin II (-1.75 versus -1.28, p = 0.01). Death by day 28 was 46 percent versus 54 percent, hazard ratio 0.78, 95 percent confidence interval 0.57 to 1.07, p = 0.12. Serious adverse events were reported in 60.7 percent of the angiotensin II group and 67.1 percent of the placebo group. Funded by the manufacturer.
- Renin analysis of ATHOS-3 (2020) tested whether plasma renin identifies the patients most likely to benefit, in the same trial population.
- Exploratory post-hoc analysis of ATHOS-3 (2023) looked at starting the infusion at lower background vasopressor doses.
- Real-world cohort (2022): 147 medical ICU patients on 3 or more vasopressors, 56 received angiotensin II. After propensity weighting, mortality was 86.0 percent versus 71.0 percent, not statistically significant (p = 0.16). This is observational, single centre, and confounded by the fact that the drug was given to the patients doing worst.
What this does not tell you: The pivotal trial's primary endpoint was a blood pressure number at 3 hours, not survival, and the trial was not sized to settle mortality. Everyone studied was already on high-dose vasopressors in an intensive care unit, so nothing here transfers to any other population, dose or route. There is no chronic dosing experience, no outpatient formulation, and no data of any kind on the uses that peptide marketing associates with this hormone.
Reading the research record
Angiotensin II is unusual among approved peptides because the whole of cardiology spends its time blocking it. ACE inhibitors and angiotensin receptor blockers exist to lower it, and the evidence that doing so prevents heart attacks, strokes and kidney failure runs to hundreds of thousands of randomised participants. The drug approval runs the other way, for a narrow rescue situation in which blood pressure will not hold.
The approval also shows what a surrogate endpoint buys and what it does not. The FDA accepted a blood pressure response at 3 hours, which the drug produced convincingly. Whether it keeps people alive is still open: the mortality difference in ATHOS-3 pointed in the drug's favour but crossed 1.0, and the largest real-world cohort published so far points the other way without being able to separate the drug from how sick its recipients were. Since June 2025 there has been a generic, which usually means the commercial incentive to run a properly powered mortality trial is gone.
The evidence, charted
Fig. 1 · evidence composition
5of 6 citations (83%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 5 distinct years, 2004 to 2023, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Approved
UK
Prescription
AU
Prescription
CA
Prescription
Approved in 1 of 4, prescription route in 3, not approved in 0. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2017
Angiotensin II for the Treatment of Vasodilatory Shock
ATHOS-3: 344 adults with catecholamine-resistant vasodilatory shock randomised, 321 analysed. A mean arterial pressure response at hour 3 occurred in 114 of 163 (69.9 percent) on angiotensin II and 37 of 158 (23.4 percent) on placebo, odds ratio 7.95, 95 percent confidence interval 4.76 to 13.3. Death by day 28 was 46 percent versus 54 percent, hazard ratio 0.78, 95 percent confidence interval 0.57 to 1.07. Funded by La Jolla Pharmaceutical Company.
New England Journal of Medicine - Human2020
Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial
Analysis of the ATHOS-3 population examining baseline and follow-up renin concentrations against survival, testing whether renin identifies which patients respond.
American Journal of Respiratory and Critical Care Medicine - Human2023
Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial
Exploratory post-hoc analysis of the same 344 patient trial asking whether starting angiotensin II at lower background vasopressor doses changes outcomes. Post-hoc and exploratory, so hypothesis generating only.
Critical Care - Human2022
Effectiveness of Angiotensin II for Catecholamine Refractory Septic or Distributive Shock on Mortality: A Propensity Score Weighted Analysis of Real-World Experience in the Medical ICU
Retrospective single-centre cohort of 147 patients needing 3 or more vasopressors, 56 given angiotensin II. After propensity score weighting mortality was 86.0 percent with angiotensin II and 71.0 percent without, a difference that was not statistically significant (p = 0.16), and more angiotensin II patients still required 5 or more vasopressors (45.9 versus 12.5 percent, p < 0.01). Observational, and the sicker patients were the ones given the drug.
Critical Care Explorations - Human2017
ATHOS-3: A Phase 3 Study of LJPC-501 in Patients With Catecholamine-Resistant Hypotension
Registry record for the pivotal trial: phase 3, 344 participants enrolled, completed, lead sponsor La Jolla Pharmaceutical Company. No results are posted in the registry record itself.
ClinicalTrials.gov - Review2004
Bradykinin receptor ligands: therapeutic perspectives
Review of the kinin system, which matters here because angiotensin-converting enzyme both makes angiotensin II and destroys bradykinin, so blocking it moves two peptides at once.
Nature Reviews Drug Discovery
Frequently asked questions
Is angiotensin II a peptide drug you can buy?
No. It is an intravenous prescription medicine given in intensive care units for shock that has stopped responding to standard vasopressors. Its half-life in plasma is under a minute, so there is no oral, subcutaneous or take-home form.
Does it save lives in shock?
That has not been shown. In its pivotal 344 person trial, death by day 28 was 46 percent on angiotensin II and 54 percent on placebo, a hazard ratio of 0.78 with a 95 percent confidence interval of 0.57 to 1.07, which includes no difference. What the trial did show is that the drug raises blood pressure when other vasopressors have failed.
Why do most drugs block angiotensin II if it is also a medicine?
Because chronically high angiotensin II drives high blood pressure, heart remodelling and kidney damage, and lowering it with ACE inhibitors or receptor blockers prevents events. Giving it deliberately is a short-term rescue in a collapsed circulation, which is a completely different situation from long-term blood pressure control.
Is it still marketed?
Yes. On the 11 September 2026 Drugs@FDA check, two GIAPREZA presentations were listed Prescription and one was listed Discontinued, and a generic angiotensin II acetate injection approved in June 2025 is listed Prescription.