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. 2025 Jul 23;15(1):104.
doi: 10.1186/s13613-025-01522-3.

Angiotensin II, conventional vasopressor therapy, and mortality in shock: a large, multicenter, propensity score-weighted analysis

Laurence W Busse  1   2   3 , Caitlin Ten Lohuis  4   5 , Han Xu  6 , Cooper Jannuzzo  7 , Robert H Lyles  6 , J Pedro Teixeira  8   9 , Ishan Mehta  4   5   10 , Yuan Liu  6
Affiliations

Angiotensin II, conventional vasopressor therapy, and mortality in shock: a large, multicenter, propensity score-weighted analysis

Laurence W Busse et al. Ann Intensive Care. .

Abstract

Background: Angiotensin II (Ang II) is typically used in addition to adrenergic agents and vasopressin (conventional therapy) in patients with shock, but whether its use improves outcomes is unknown.

Research question: We evaluated whether Ang II, when added to conventional therapy at different norepinephrine equivalent (NE) doses, was associated with mortality.

Methods: We performed a retrospective analysis of 811 patients admitted to four centers in a single healthcare system who received vasopressors for shock, including 275 who received Ang II plus conventional therapy and 536 who received only conventional therapy. Age, gender, sequential organ failure assessment score, serum lactate, background NE dose, corticosteroid use, pre-morbid angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and Charlson Comorbidity Index were calculated at initiation of Ang II or at an equivalent point of acuity in the conventional therapy cohort. We used propensity scores with inverse probability of treatment weighting (IPTW) to achieve covariate balance and multivariable logistic regression to compare 30-day mortality, further stratifying patients by 0.10 mcg/kg/min NE increments.

Results: Overall 30-day mortality was 56.4%. Groups statistically differed by all baseline variables. In multivariable logistic regression, Ang II treatment was associated with lower 30-day mortality compared to conventional therapy alone (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.45-0.95, p = 0.025). After IPTW, Ang II use was independently associated with lower mortality (OR 0.74, 95% CI 0.55-0.99, p = 0.040). When stratifying by increments of background NE dose, Ang II initiation was associated with lower 30-day mortality compared to conventional therapy alone in patients on background NE doses > 0.4, > 0.5, and ≤ 0.6 mcg/kg/min. Ang II use in patients on background NE dose > 0.6 was not significantly associated with mortality.

Conclusions: Ang II administration was associated with a lower risk of death in unadjusted and adjusted analyses. This effect was preserved only with patients receiving NE at doses ranging from 0.4 to 0.6 mcg/kg/min. Though additional prospective studies are required, these findings suggest that Ang II may be beneficial across a specific range of background vasopressor doses.

Keywords: Angiotensin II; Renin-angiotensin system; Sepsis; Shock; Vasopressors.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was reviewed by the Emory University Institutional Review Board (IRB00113240) and conducted in accordance with all applicable laws and local regulations, including Protection of Human Volunteers (21 CFR 50), Institutional Review Boards (21 CFR 56), and Obligations of Clinical Investigators (21 CFR 312) with a waiver of consent. Consent for publication: Not applicable. Competing interests: LWB reports no conflict of interest. CTL reports no conflict of interest. HX reports no conflict of interest. CJ reports no conflict of interest. RHL reports no conflict of interest. JPT reports receiving consulting fees from Outset Medical and owns stock or options in Eli Lilly, Novo Nordisk A/S, and Pfizer. IM reports no conflict of interest. YL reports no conflict of interest.

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