Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial

Authors

• Patrick M. Wieruszewski, Departments of Pharmacy and Anesthesiology, Mayo Clinic, Rochester, MN, USA.
• Rinaldo Bellomo, Department of Critical Care, Melbourne Medical School, University of Melbourne, Parkville, Australia.
• Laurence W. Busse, Department of Medicine, Emory University, Atlanta, GA, USA.
• Kealy R. Ham, Department of Critical Care Medicine, Mayo Clinic Arizona, Phoenix, AZ, USA.
• Alexander Zarbock, Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, University Münster, Munster, Germany.
• Ashish K. Khanna, Department of Anesthesiology, Section on Critical Care Medicine, Wake Forest School of Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
• Adam M. Deane, Department of Critical Care, Melbourne Medical School, University of Melbourne, Parkville, Australia.
• Marlies Ostermann, Department of Critical Care, King's College London, Guy's and St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK.
• Richard G. Wunderink, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
• David W. Boldt, Department of Anesthesiology and Critical Care Medicine, University of California Los Angeles, Los Angeles, CA, USA.
• Stew Kroll, La Jolla Pharmaceutical Company, Waltham, MA, USA.
• Chuck R. Greenfeld, La Jolla Pharmaceutical Company, Waltham, MA, USA.
• Tony Hodges, La Jolla Pharmaceutical Company, Waltham, MA, USA.
• Jonathan H. Chow, Department of Anesthesiology and Critical Care Medicine, George Washington University School of Medicine and Health Sciences, 2700 M St. NW, 7Th Floor, Room 709, Washington, DC, 20037, USA. JChow@mfa.gwu.edu.

Document Type

Journal Article

Publication Date

5-5-2023

Journal

Critical care (London, England)

Volume

27

Issue

1

DOI

10.1186/s13054-023-04446-1

Keywords

Angiotensin; Catecholamine; Multimodal; Outcomes; Shock; Vasopressor

Abstract

BACKGROUND: High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II). METHODS: Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized 321 patients with vasodilatory shock, who remained hypotensive (mean arterial pressure of 55-70 mmHg) despite receiving standard of care vasopressor support at a norepinephrine-equivalent dose (NED) > 0.2 µg/kg/min, to receive AT II or placebo, both in addition to standard of care vasopressors. Patients were grouped into low (≤ 0.25 µg/kg/min; n = 104) or high (> 0.25 µg/kg/min; n = 217) NED at the time of study drug initiation. The primary outcome was the difference in 28-day survival between the AT II and placebo subgroups in those with a baseline NED ≤ 0.25 µg/kg/min at the time of study drug initiation. RESULTS: Of 321 patients, the median baseline NED in the low-NED subgroup was similar in the AT II (n = 56) and placebo (n = 48) groups (median of each arm 0.21 µg/kg/min, p = 0.45). In the high-NED subgroup, the median baseline NEDs were also similar (0.47 µg/kg/min AT II group, n = 107 vs. 0.45 µg/kg/min placebo group, n = 110, p = 0.75). After adjusting for severity of illness, those randomized to AT II in the low-NED subgroup were half as likely to die at 28-days compared to placebo (HR 0.509; 95% CI 0.274-0.945, p = 0.03). No differences in 28-day survival between AT II and placebo groups were found in the high-NED subgroup (HR 0.933; 95% CI 0.644-1.350, p = 0.71). Serious adverse events were less frequent in the low-NED AT II subgroup compared to the placebo low-NED subgroup, though differences were not statistically significant, and were comparable in the high-NED subgroups. CONCLUSIONS: This exploratory post-hoc analysis of phase 3 clinical trial data suggests a potential benefit of AT II introduction at lower doses of other vasopressor agents. These data may inform design of a prospective trial. TRIAL REGISTRATION: The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015.

APA Citation

Wieruszewski, Patrick M.; Bellomo, Rinaldo; Busse, Laurence W.; Ham, Kealy R.; Zarbock, Alexander; Khanna, Ashish K.; Deane, Adam M.; Ostermann, Marlies; Wunderink, Richard G.; Boldt, David W.; Kroll, Stew; Greenfeld, Chuck R.; Hodges, Tony; and Chow, Jonathan H., "Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial" (2023). GW Authored Works. Paper 2940.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2940

Department

Anesthesiology and Critical Care Medicine