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Author Notes:

Kealy R. Ham: Kealy.R.Ham@HealthPartners.com Division of Critical Care Medicine, Regions Hospital, University of Minnesota, 640 Jackson Street, St. Paul, MN 55101, USA

KRH, DWB, MTM, and LWB helped interpret the results of the analyses and were major contributors in writing of the manuscript.

RF, MNG, AKK, SNC, and MO were major contributors in providing interpretation of the data.

FZ, LSC, and GFT were involved in the acquisition and analysis of the data.

All authors read and approved the final manuscript and have agreed to be accountable for the work.

Medical writing and editorial assistance was provided by Jerome Sah, PhD, of ApotheCom, Yardley, PA, USA.

KRH reports no conflict of interest; DWB received consulting payment from La Jolla Pharmaceutical Company and received grant/payment to his institution from La Jolla Pharmaceutical Company; MTM is on the speakers bureau for La Jolla Pharmaceutical Company, and his institution received a grant for its role as a participating site in the ATHOS-3 trial; LWB reports payment for consulting work from La Jolla Pharmaceutical Company; RF reports nothing to disclose; MNG reports payment to her institution for the conduct of the trials in the form of a contract to perform the study; AKK reports payment from La Jolla Pharmaceutical Company for consulting work and participation in the company’s speakers bureau; SNC reports nothing to disclose; LSC and GFT are employees of La Jolla Pharmaceutical Company; MO and FZ report nothing to disclose.


Research Funding:

These analyses and the original study were funded by La Jolla Pharmaceutical Company.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Critical Care Medicine
  • General & Internal Medicine
  • Shock
  • Hypotension
  • Angiotensin II
  • Dose response
  • Septic shock

Sensitivity to angiotensin II dose in patients with vasodilatory shock: a prespecified analysis of the ATHOS-3 trial

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Journal Title:

Annals of Intensive Care


Volume 9, Number 1


, Pages 63-63

Type of Work:

Article | Final Publisher PDF


Background: Early clinical data showed that some patients with vasodilatory shock are responsive to low doses of angiotensin II. The objective of this analysis was to compare clinical outcomes in patients requiring ≤ 5 ng kg−1 min−1 angiotensin II at 30 min (≤ 5 ng kg−1 min−1 subgroup) to maintain mean arterial pressure (MAP) ≥ 75 mmHg versus patients receiving > 5 ng kg−1 min−1 angiotensin II at 30 min (> 5 ng kg−1 min−1 subgroup). Data from angiotensin II-treated patients enrolled in the ATHOS-3 trial were used. Results: The subgroup of patients whose angiotensin II dose was down-titrated from 20 ng kg−1 min−1 at treatment initiation to ≤ 5 ng kg−1 min−1 at 30 min (79/163) had significantly lower endogenous serum angiotensin II levels and norepinephrine-equivalent doses and significantly higher MAP versus the > 5 ng kg−1 min−1 subgroup (84/163). Patients in the ≤ 5 ng kg−1 min−1 subgroup were more likely to have a MAP response at 3 h versus those in the > 5 ng kg−1 min−1 subgroup (90% vs. 51%, respectively; odds ratio, 8.46 [95% CI 3.63–19.7], P < 0.001). Day 28 survival was also higher in the ≤ 5 ng kg−1 min−1 subgroup versus the > 5 ng kg−1 min−1 subgroup (59% vs. 33%, respectively; hazard ratio, 0.48 [95% CI 0.28–0.72], P = 0.0007); multivariate analyses supported the survival benefit in patients with lower angiotensin II levels. The ≤ 5 ng kg−1 min−1 subgroup had a more favorable safety profile and lower treatment discontinuation rate than the > 5 ng kg−1 min−1 subgroup. Conclusions: This prespecified analysis showed that down-titration to ≤ 5 ng kg−1 min−1 angiotensin II at 30 min is an early predictor of favorable clinical outcomes which may be related to relative angiotensin II insufficiency.

Copyright information:

© 2019, The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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