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Dr. Grey AI

Peptide

Angiotensin II

Angiotensin II is the endogenous vasoconstrictor peptide now available as a synthetic IV formulation (Giapreza). FDA-approved 2017 for vasodilatory/septic shock refractory to standard vasopressors. A-GRADE evidence from ATHOS-3 (n=321): 70% achieved MAP response vs 23% placebo (P<0.001). Post-hoc analysis: AKI patients on RRT showed 53% vs 30% survival at day 28. SAFETY CONCERN: Increased thromboembolism (13% vs 5%), requires DVT prophylaxis. No mortality benefit in main analysis - approved for hemodynamic response, not survival. PRESCRIPTION ONLY - ICU setting.

Research notice. This page is for education and research. Peptides may not be FDA-approved for human use and may only be legally available for research. Talk to a qualified clinician before considering any peptide.

Best evidence
Grade A
Conditions studied
2
Outcomes
12
Graded outcomes
4224

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

2 conditions, plus general outcomes

Septic Shock

Septic Shock: outcomes studied for Angiotensin II
GradeOutcomeEffectSizeStudiesPeopleStudies list
Thromboembolic Events

SAFETY CONCERN: ATHOS-3: 13% vs 5% thromboembolic events (DVT, arterial). Major imbalance in DVT. Concurrent DVT prophylaxis required. Systematic review (n=1,461): Similar rates in larger observational data (8.8% vs 9.4% VTE).

Worsens (the measure goes down)Moderate effect51 studies

Studies that measured thromboembolic events

and 41 more in the citations list

Mean Arterial Pressure Response

ATHOS-3 (n=321): 70% achieved MAP ≥75 mmHg or ≥10 mmHg increase at 3h vs 23% placebo (P<0.001). 45% absolute increase in responders. Effective in catecholamine-resistant shock.

Improves (the measure goes up)Large effect50 studies

Studies that measured mean arterial pressure response

and 40 more in the citations list

Vasopressor Dose Reduction

ATHOS-3: Significant reduction in background vasopressor requirements. Catecholamine-sparing effect allows reduction of norepinephrine doses. May reduce catecholamine toxicity.

Improves (the measure goes down)Moderate effect50 studies

Studies that measured vasopressor dose reduction

and 40 more in the citations list

28-Day Mortality

ATHOS-3: No significant mortality difference (46% vs 54%, P=0.12). Study not powered for mortality. Post-hoc AKI/RRT subgroup: 53% vs 30% survival (P=0.012). Mortality benefit uncertain.

NoneNo effect50 studies

Studies that measured 28-day mortality

and 40 more in the citations list

Acute Kidney Injury

Acute Kidney Injury: outcomes studied for Angiotensin II
GradeOutcomeEffectSizeStudiesPeopleStudies list
Renal Recovery in AKI

Post-hoc ATHOS-3 (n=105): Higher RRT liberation rate and 28-day survival (53% vs 30%, P=0.012) in AKI patients. May preferentially benefit those with renal failure. Requires prospective validation.

Improves (the measure goes up)Moderate effect50 studies

Studies that measured renal recovery in aki

and 40 more in the citations list

General

General: outcomes studied for Angiotensin II
GradeOutcomeEffectSizeStudiesPeopleStudies list
Cardiac Protection

5 human trials support this finding. Human clinical trial data available.

Improves (the measure goes up)Small effect6 studies

Studies that measured cardiac protection

Kidney Function

10 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Moderate effect11 studies

Studies that measured kidney function

and 1 more in the citations list

Blood Pressure

6 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes down)Small effect7 studies

Studies that measured blood pressure

Anti-Cancer Activity

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect3 studies

Studies that measured anti-cancer activity

Muscle Mass/Function

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect3 studies

Studies that measured muscle mass/function

Cancer Cell Apoptosis

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect3 studies
Anti-Inflammatory Activity

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect3 studies

Key findings

  • Thromboembolic EventsSeptic ShockWorsens (the measure goes down)
  • Mean Arterial Pressure ResponseSeptic ShockImproves (the measure goes up)
  • Vasopressor Dose ReductionSeptic ShockImproves (the measure goes down)

Safety notes in the studies

  • May reduce catecholamine toxicity.

Studies cited

37 studies from PubMed

  1. Angiotensin-II and Thromboembolic Events: A Systematic ReviewPharmacotherapy, 2024 · PMID 39637259
  2. Angiotensin II Is Involved in MLKL Activation During the Development of Heart Failure Following Myocardial Infarction in Rats.Biological & pharmaceutical bulletin, 2024 · PMID 38583954
  3. The Role of Local Angiotensin II/Angiotensin Type 1-receptor Mechanisms in Adipose Tissue Dysfunction to Promote Pancreatic Cancer.Current cancer drug targets, 2024 · PMID 38347780
  4. Roles of autophagy in angiotensin II-induced cardiomyocyte apoptosis.Clinical and experimental pharmacology & physiology, 2022 · PMID 36059129
  5. Angiotensin II (Giapreza): A Distinct Mechanism for the Treatment of Vasodilatory ShockCardiol Rev, 2019 · PMID 30601161
  6. FDA Approval of Angiotensin II for the Treatment of Hypotension in Adults with Distributive ShockAm J Cardiovasc Drugs, 2019 · PMID 30179724
  7. Association Between Early Response to Angiotensin-II and Mortality in Septic Shock: A Post Hoc Analysis of the ATHOS-III Clinical TrialCrit Care, 2019 · PMID 31061651
  8. Renin-Angiotensin System in the Intensive Care UnitSemin Nephrol, 2019 · PMID 30806453
  9. Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin IICrit Care Med, 2018 · PMID 29925534
  10. Angiotensin II: a new therapeutic option for vasodilatory shockCrit Care, 2018 · PMID 29958101
  11. Angiotensin II Brings More Questions Than AnswersCrit Care Med, 2018 · PMID 30272566
  12. Angiotensin II and Treatment of High-Output Shock in Human Beings: A Matched Case SeriesClin Pharmacol Ther, 2018 · PMID 29482879
  13. Vasodilatory shock in the ICU and the role of angiotensin II.Current opinion in critical care, 2018 · PMID 29877879
  14. Angiotensin II for the Treatment of Vasodilatory ShockN Engl J Med, 2017 · PMID 28528561
  15. Angiotensin II type 1a receptor-deficient mice develop angiotensin II-induced oxidative stress and DNA damage without blood pressure increase.American journal of physiology. Renal physiology, 2017 · PMID 28877878
  16. Angiotensin II and skeletal muscle abnormalities.Experimental physiology, 2017 · PMID 28568964
  17. Angiotensin (1-7) receptor antagonism equalizes angiotensin II-induced hypertension in male and female spontaneously hypertensive rats.Hypertension (Dallas, Tex. : 1979), 2010 · PMID 20713916
  18. Angiotensin II-nitric oxide interaction in the kidney.Current opinion in nephrology and hypertension, 2007 · PMID 17143071
  19. Angiotensin II type 2 receptor decreases ischemia reperfusion induced fluid leak.The Journal of surgical research, 2007 · PMID 17291529
  20. Angiotensin II and renal tubular ion transport.TheScientificWorldJournal, 2005 · PMID 16142301
  21. Angiotensin II, angiotensin II antagonists and spironolactone and their modulation of cardiac repolarization.Trends in pharmacological sciences, 2005 · PMID 15749161
  22. Angiotensin-II behaves as an endogenous pro-inflammatory molecule.The Journal of the Association of Physicians of India, 2005 · PMID 16124358
  23. Protective effects of angiotensin II interruption: evidence for antiinflammatory actions.Pharmacotherapy, 2005 · PMID 16164395
  24. Cardiac angiotensin II: an intracrine hormone?American journal of hypertension, 2002 · PMID 12460709
  25. Angiotensin II as a mediator of renal tubular transport.Contributions to nephrology, 2001 · PMID 11705291
  26. Angiotensin II induces phenotype-dependent apoptosis in vascular smooth muscle cells.Hypertension (Dallas, Tex. : 1979), 2001 · PMID 11751706
  27. Angiotensin II receptor blockers: review of the binding characteristics.The American journal of cardiology, 1999 · PMID 10588088
  28. Angiotensin II receptors in the kidney.Kidney & blood pressure research, 1998 · PMID 9762845
  29. Biology and functions of renal receptors for angiotensin II and its active fragments.Advances in nephrology from the Necker Hospital, 1998 · PMID 9889993
  30. Angiotensin II receptors on colorectal carcinoma cells.International journal of molecular medicine, 1998 · PMID 9858658
  31. Regional angiotensin II production in essential hypertension and renal artery stenosis.Hypertension (Dallas, Tex. : 1979), 1993 · PMID 8428780
  32. The intrarenal renin-angiotensin system.Current opinion in nephrology and hypertension, 1993 · PMID 7922165
  33. Angiotensin II receptor subtypes in the kidney.Journal of the American Society of Nephrology : JASN, 1993 · PMID 8318680
  34. Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts.Circulation research, 1993 · PMID 8495553
  35. Angiotensin II and renal hypertension in dog, rat and man: effect of converting enzyme inhibition.Clinical and experimental hypertension, 1980 · PMID 6253241
  36. [Angiotensin II analogue and essential hypertension].Nihon rinsho. Japanese journal of clinical medicine, 1979 · PMID 392137
  37. Angiotensin II in arterial and renal venous plasma and renal lymph in the dog.The Journal of clinical investigation, 1971 · PMID 4322664