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Why RAAS

RAAS dysfunction
can contribute to
persistent hypotension1

Jump to:

Traditional
vasopressors

Catecholamines and vasopressin can leave too
many patients at life-threatening risk2

The longer hypotension persists, the higher the mortality risk2,*

If low MAP persists for 0 to 2 hours, mortality risk can reach up to 31%2

If low MAP persists for 6 to 8 hours, mortality risk can reach up to 75%2

*From a retrospective analysis of 5,347 patients with vasodilatory (distributive) shock who received fluid resuscitation and vasopressors, including norepinephrine, epinephrine, dopamine, phenylephrine, and/or vasopressin.2

Vasoregulatory
Systems

RAAS provides a complementary pathway for MAP regulation3-6

Traditional vasopressors address the adrenergic and vasopressin systems that regulate blood pressure, neglecting RAAS, the third essential vasoregulatory system.3-6

RAAS produces ANG II, a naturally occurring peptide hormone that triggers vasoconstriction and increases blood pressure.1,7

GIAPREZA is the first and only synthetic human ANG II treatment—the only RAAS regulator available to stabilize MAP in adults with septic and vasoplegic shock.4-9

RAAS, vasopressin, and adrenal systems regulate MAP
##

Targeting RAAS

Only GIAPREZA stabilizes
MAP via RAAS1

In patients with septic or vasoplegic shock, the RAAS pathway may be disrupted by an ACE deficiency, leading to abnormally high ANG I/II ratios and ANG (1–7) levels. This disruption can result in increased catecholamine use and can trap patients in a potentially fatal cycle of persistent hypotension.1

Slide image to view more

Diagram of how RAAS pathway molecules work to increase vasoconstriction and how dysfunction in the pathway leads to hypotensionDiagram of how RAAS pathway molecules work to increase vasoconstriction and how dysfunction in the pathway leads to hypotension
Diagram of how RAAS pathway molecules work to increase vasoconstriction and how dysfunction in the pathway leads to hypotension

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ACE=angiotensin-converting enzyme; AGT=angiotensinogen; ANG=angiotensin; MAP=mean arterial pressure.

References:

  1. Bellomo R, Forni LG, Busse LW, et al. Renin and survival in patients given angiotensin II for catecholamine-resistant vasodilatory shock. A clinical trial. Am J Respir Crit Care Med. 2020;202(9):1253-1261. doi:10.1164/rccm.201911-2172OC
  2. Vincent JL, Nielsen ND, Shapiro NI, et al. Mean arterial pressure and mortality in patients with distributive shock: a retrospective analysis of the MIMIC-III database. Ann Intensive Care. 2018;8(1):107. doi:10.1186/s13613-018-0448-9
  3. Klijian A, Khanna AK, Reddy VS, et al. Treatment with angiotensin II is associated with rapid blood pressure response and vasopressor sparing in patients with vasoplegia after cardiac surgery: a post-hoc analysis of Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. J Cardiothorac Vasc Anesth. 2021;35(1):51-58. doi:10.1053/j.jvca.2020.08.001
  4. Khalil B, Rosani A, Warrington SJ. Physiology, Catecholamines. StatPearls; 2024. Accessed August 21, 2026. https://www.ncbi.nlm.nih.gov/books/NBK507716/
  5. Demiselle J, Fage N, Radermacher P, et al. Vasopressin and its analogues in shock states: a review. Ann Intensive Care. 2020;10(1):9. doi:10.1186/s13613-020-0628-2
  6. National Center for Biotechnology Information. PubChem Compound Summary for CID 172198, angiotensin II. Accessed August 21, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/Angiotensin-II-human
  7. GIAPREZA. Prescribing information. La Jolla Pharmaceutical Company; 2021.
  8. Richards E, Lopez MJ, Maani CV. Phenylephrine. In: StatPearls. StatPearls Publishing; updated October 30, 2023. Accessed June 10, 2026. https://www.ncbi.nlm.nih.gov/books/NBK534801/
  9. Ashkar H, Adnan G, Patel P, et al. Dobutamine. In: StatPearls. StatPearls Publishing; updated February 23, 2024. Accessed June 10, 2026. https://www.ncbi.nlm.nih.gov/books/NBK470431/
  10. Andrews L, Benken J, Benedetti E, et al. Effects of angiotensin II in the management of perioperative hypotension in kidney transplant recipients. Clin Transplant. 2022;36(9):e14754. doi:10.1111/ctr.14754
  11. Fountain JH, Kaur J, Lappin SL. Physiology, Renin Angiotensin System. StatPearls; 2023. Accessed January 14, 2026. https://www.ncbi.nlm.nih.gov/books/NBK470410/
  12. Wang Y, Seto S-W, Golledge J. Angiotensin II, sympathetic nerve activity and chronic heart failure. Heart Fail Rev. 2014;19:187-198. doi:10.1007/s10741-012-9368-1
  13. Bitker L, Burrell LM. Classic and nonclassic renin-angiotensin systems in the critically ill. Crit Care Clin. 2019:35(2):213-227. doi:10.1016/j.ccc.2018.11.002
  14. Buckley MS, Barletta JF, Smithburger PL, et al. Catecholamine vasopressor support sparing strategies in vasodilatory shock. Pharmacotherapy. 2019;39(3):382-398. doi:10.1002/phar.2199
  15. Supplementary appendix to: Khanna A, English SW, Wang XS, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377(5):419-430. doi:10.1056/NEJMoa1704154
  16. Khanna A, English SW, Wang XS, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377(5):419-430. doi:10.1056/NEJMoa1704154

INDICATION

GIAPREZA® (angiotensin II) increases blood pressure in adults with septic or other distributive shock.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

The safety of GIAPREZA was evaluated in 321 adults with septic or other distributive shock in a randomized, double-blind, placebo-controlled study, ATHOS-3. There was a higher incidence of arterial and venous thrombotic and thromboembolic events in patients who received GIAPREZA compared to placebo-treated patients in the ATHOS-3 study (13% vs. 5%). The major imbalance was in deep venous thromboses. Use concurrent venous thromboembolism (VTE) prophylaxis.

Adverse Reactions

The most common adverse reactions reported in greater than 10% of GIAPREZA-treated patients were thromboembolic events. Adverse reactions occurring in ≥4% of patients treated with GIAPREZA and ≥1.5% more often than placebo-treated patients in the ATHOS-3 study were thromboembolic events (including deep vein thrombosis), thrombocytopenia, tachycardia, fungal infection, delirium, acidosis, hyperglycemia, and peripheral ischemia.

Drug Interactions

Angiotensin converting enzyme (ACE) inhibitors may increase response to GIAPREZA. Angiotensin II receptor blockers (ARBs) may reduce response to GIAPREZA.

You are encouraged to report negative side effects of prescription drugs to the FDA. To report SUSPECTED ADVERSE REACTIONS, please contact:

La Jolla Pharmaceutical Company

1-800-651-3861

medicalinformation@ljpc.com

U.S. Food and Drug Administration

1-800-FDA-1088

www.fda.gov/medwatch

Before administering, please see the Full Prescribing Information for GIAPREZA.

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Innoviva Specialty Therapeutics

GIAPREZA® is marketed by Innoviva Specialty Therapeutics, Inc. in partnership with La Jolla Pharmaceutical Company.

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