Angiotensin II for the Treatment of Vasodilatory Shock



Khanna, Ashish, English, Shane W, Wang, Xueyuan S, Ham, Kealy, Tumlin, James, Szerlip, Harold, Busse, Laurence W, Altaweel, Laith, Albertson, Timothy E, Mackey, Caleb
et al (show 20 more authors) (2017) Angiotensin II for the Treatment of Vasodilatory Shock. NEW ENGLAND JOURNAL OF MEDICINE, 377 (5). pp. 419-430.

[img] Text
nejmoa1704154_appendix.pdf - Published version

Download (714kB)
[img] Text
AngII_2017_nejmoa1704154.pdf - Published version

Download (281kB)

Abstract

<h4>Background</h4>Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition.<h4>Methods</h4>We randomly assigned patients with vasodilatory shock who were receiving more than 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 end point 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 at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors.<h4>Results</h4>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 end point 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 to 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 to 1.07; P=0.12).<h4>Conclusions</h4>Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843 .).

Item Type: Article
Uncontrolled Keywords: ATHOS-3 Investigators, Humans, Hypotension, Shock, Catecholamines, Angiotensin II, Vasoconstrictor Agents, Drug Therapy, Combination, Double-Blind Method, Blood Pressure, Aged, Middle Aged, Female, Male, Organ Dysfunction Scores
Depositing User: Symplectic Admin
Date Deposited: 11 Oct 2017 09:45
Last Modified: 19 Jan 2023 06:53
DOI: 10.1056/NEJMoa1704154
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3009931