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Angiotensin II
Angiotensin II (Giapreza) is a real, FDA-approved peptide drug for septic and other vasodilatory shock — genuinely novel in that it's the exact endogenous human peptide itself, not an analog, and it's approved on a hemodynamic surrogate endpoint rather than a proven mortality benefit.
Evidence grade B: what kinds of studies support the claims on this page, with limits. It is not a verdict on any product. How we grade
On this page
In brief
Should you care? Only relevant if you or someone you know is in intensive care for septic or vasodilatory shock — this is a hospital-only drug with no wellness or grey-market angle at all.The short version
- The exact native peptide — synthetic human angiotensin II, chemically identical to what your body already makes, not an analog.
- ATHOS-3 trial: met its hemodynamic endpoint clearly (69.9% vs. 23.4% blood-pressure response) but the mortality difference was not statistically significant (46% vs. 54%, p=0.12).
- Real thrombosis risk — 13% vs. 5% for placebo — requiring blood-clot prevention alongside treatment.
What makes it novel
Angiotensin II is a synthetic 8-amino-acid peptide, chemically identical to the endogenous human hormone of the same name — not a modified analog, which is unusual for an approved peptide drug. It works as a direct vasoconstrictor via the angiotensin II type 1 (AT1) receptor, essentially activating the renin-angiotensin-aldosterone system pharmacologically to raise blood pressure in patients whose blood vessels have become dangerously dilated despite standard vasopressor treatment.
The ATHOS-3 trial, and what it did and didn't show
The FDA approved angiotensin II (as Giapreza) on 21 December 2017 based on the ATHOS-3 trial (Khanna et al., N Engl J Med 2017, PMID 28528561): 321 adults with catecholamine-refractory vasodilatory shock (91% septic shock), randomized to angiotensin II or placebo added to standard vasopressors. The primary endpoint — a meaningful blood-pressure response at 3 hours — was clearly met: 69.9% of the angiotensin II group responded versus 23.4% on placebo (p<0.001). The honest caveat: 28-day mortality, a secondary endpoint, was numerically lower with angiotensin II (46% vs. 54%) but the difference was not statistically significant (p=0.12). This is an approval built on a hemodynamic surrogate endpoint, not a proven survival benefit — a later post-hoc subgroup analysis (not part of the original approval) suggested a possible mortality benefit specifically in patients with severe acute kidney injury, but that finding is exploratory and hasn't been independently confirmed.
Safety
The clearest safety signal from ATHOS-3 was a higher rate of thrombotic and thromboembolic events with angiotensin II than placebo (13% vs. 5%), largely deep vein thrombosis — the label recommends concurrent blood-clot prevention unless contraindicated. We could not confirm whether Giapreza carries a boxed (black-box) warning specifically versus only a Warnings and Precautions section on this point; check the current label directly if that distinction matters to you.
Current status
Still marketed, now by Innoviva (which acquired original developer La Jolla Pharmaceutical Company in 2022). This is a hospital/ICU-only IV infusion with no oral, injectable-at-home, or grey-market form, and no relevance to the wellness or grey-market peptide market this site otherwise covers extensively.
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References
- Khanna A, English SW, Wang XS, et al. (ATHOS-3 Investigators), "Angiotensin II for the Treatment of Vasodilatory Shock," N Engl J Med 2017;377(5):419-430, PMID 28528561, DOI: 10.1056/NEJMoa1704154.
- FDA approval history for Giapreza (angiotensin II), initial approval 21 December 2017.