Initiating angiotensin II at lower vasopressor doses in vasodilatory shock : an exploratory post-hoc analysis of the ATHOS-3 clinical trial
© 2023. The Author(s)..
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.
Errataetall: |
CommentIn: Crit Care. 2023 May 30;27(1):210. - PMID 37254175 |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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Enthalten in: |
Critical care (London, England) - 27(2023), 1 vom: 05. Mai, Seite 175 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Wieruszewski, Patrick M [VerfasserIn] |
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Links: |
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Themen: |
11128-99-7 |
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Anmerkungen: |
Date Completed 22.05.2023 Date Revised 30.05.2023 published: Electronic ClinicalTrials.gov: NCT02338843 CommentIn: Crit Care. 2023 May 30;27(1):210. - PMID 37254175 Citation Status MEDLINE |
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doi: |
10.1186/s13054-023-04446-1 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM356508579 |
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245 | 1 | 0 | |a Initiating angiotensin II at lower vasopressor doses in vasodilatory shock |b an exploratory post-hoc analysis of the ATHOS-3 clinical trial |
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500 | |a CommentIn: Crit Care. 2023 May 30;27(1):210. - PMID 37254175 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2023. The Author(s). | ||
520 | |a 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) | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a TRIAL REGISTRATION: The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015 | ||
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