Leisman, D. E., Wieruszewski, P. M., Busse, L. W., et al. | Crit Care (2025) 29(1):81 | An index of the initial blood pressure response to angiotensin II treatment and its association with clinical outcomes in vasodilatory shock- Outcomes Research Consortium

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Leisman, D. E., Wieruszewski, P. M., Busse, L. W., et al. | Crit Care (2025) 29(1):81 | An index of the initial blood pressure response to angiotensin II treatment and its association with clinical outcomes in vasodilatory shock

November 29, 2025

Background: No standardized index exists to assess cardiovascular responsiveness to angiotensin-II. We hypothesized
that a standardized index of initial blood pressure response to angiotensin-II treatment would be associated with clini-
cal outcomes.
Methods: Using data from the Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we developed an Angi-
otensin-II Initial MAP Response Index of Treatment Effect (AIMRITE) defined as (MAP at hr1 – MAP at baseline)/study
drug dose. We assessed AIMRITE continuously and, based on observed distributions, we additionally categorized
patients as “responsive” or “resistant”, with responsiveness defined by an AIMRITE ≥ 0.90 mmHg/ng/kg/min. The
primary clinical outcome was 28-day mortality. Secondary outcomes included days alive and vasopressor- or ventila-
tor- or renal replacement therapy-free at day-7. Biological outcomes included baseline renin, angiotensin-II, and renin/
angiotensin-II ratio, and their change at hr3.
Results: Of 158 placebo patients, as expected, 157 (99%) had AIMRITE < 0.90 mmHg/ng/kg/min (median AIMRITE 0.02; IQR − 0.03–0.10). In contrast, 163 patients assigned to angiotensin-II had a median AIMRITE of 1.43 mmHg/ ng/kg/min (IQR 0.35–2.83). Of these, 97 (60%) were responsive (median AIMRITE 2.55; IQR 1.66–4.12) and 66 (40%) were resistant (median AIMRITE 0.24; IQR 0.10–0.52). Each 1.0-unit increase in AIMRITE was associated with a 16% lower hazard of death (HR: 0.84 per mmHg/ng/kg/min [95% CI 0.74–0.95], p=0.0062). Responsive patients had half the mortality hazard than resistant patients (HR: 0.50 [95% CI 0.32–0.78], p=0.0026) and placebo patients (HR 0.58[95% CI 0.40–0.86], p=0.0064). Resistant patients had a similar mortality hazard to placebo (HR 1.17 [95% CI 0.80–1.72],p=0.41). Compared to resistant patients, responsive patients had lower baseline renin and renin/angiotensin-II ratio, but a greater decrease in both at hr3. When stratified by baseline renin level, mortality was highest in placebo patients with high renin (69%) and angiotensin-II resistant patients with low renin (61%).