Angiotensin II for Treatment of Vasodilatory Shock

Study Questions:

What is the effectiveness of angiotensin II for the treatment of patients with vasodilatory shock?


The ATHOS-3 (Angiotensin II for the Treatment of High-Output Shock) investigators randomly assigned patients with vasodilatory shock who were receiving >0.2 μg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary endpoint was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of ≥10 mm Hg or an increase to ≥75 mm Hg, without an increase in the dose of background vasopressors.


A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary endpoint was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76-13.3; p < 0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (−1.75 vs. −1.28, p = 0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57-1.07; p = 0.12).


The authors concluded that angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors.


This randomized, controlled trial involving patients with vasodilatory shock who were receiving high doses of conventional vasopressors, reports significantly greater blood pressure and lower requirements for catecholamines in the angiotensin II group than in the placebo group. Furthermore, cardiovascular SOFA scores, which quantify catecholamine use, were significantly lower in the angiotensin group than in the placebo group at 48 hours. While these preliminary results are promising, larger trials with longer duration of follow-up are needed to address mortality benefits, along with direct comparisons of angiotensin II with other vasopressors.

Clinical Topics: Prevention, Hypertension

Keywords: Angiotensin II, Blood Pressure, Blood Pressure Determination, Catecholamines, Hypertension, Norepinephrine, Primary Prevention, Shock, Vasoconstrictor Agents, Vascular Diseases

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