6: Effect of Disease Severity on Survival in Patients Receiving Angiotensin Ii for Vasodilatory Shock

Szerlip, Harold M.; Bïhorac, Azra; Chang, Steven Y.; Chung, Kyungsoon; Hästbacka, Johanna; Murugan, Raghavan; Favory, Raphaël; Tumlin, James A.; Venkatesh, Balasubramanian; Chawla, Lakhmir S.; Tidmarsh, George F.

doi:10.1097/01.ccm.0000528062.45598.be

Cited by 23 publications

(10 citation statements)

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“…These results are statistically and clinically important because, contemporary evidence examining the use of human Ang-2 is mainly from the ATHOS-3 trial and its subsequent post-hoc analyses. 3,[9][10][11][12][13][14][15][16] Our study includes patients with a wide variety of shock states, including cardiogenic and hypovolemic shock, which were not studied in ATHOS-3.…”

Section: Discussionmentioning

confidence: 99%

“…Although this was a multicenter study, the heterogeneity and volume of patients limits our ability to perform subgroup analyses and to definitively draw conclusions about mortality in certain populations where there could be incremental benefit. [9][10][11][12] Furthermore, our study did not have a separate control group for comparison. Instead each patient served as their own internal control, and we observed hemodynamics and vasopressor dose before and after treatment with Ang-2.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8] Since the ATHOS and ATHOS-3 trials, several subgroup analyses have been performed of ATHOS-3, which demonstrated mortality benefit in particular patient populations. [9][10][11][12] With the exception of case reports, small case series, and 1 multicenter study, studies occurring after ATHOS-3 that have not been derived from that study's dataset are sparse. [13][14][15][16][17] The purpose of our multicenter study was to assess the effectiveness of Ang-2 for the treatment of shock.…”

Section: Introductionmentioning

confidence: 99%

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A Multicenter Observational Cohort Study of Angiotensin II in Shock

Smith

Newsome

Guo

et al. 2020

J Intensive Care Med

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Introduction: Angiotensin II (Ang-2) is a non-catecholamine vasopressor that targets the renin-angiotensin-aldosterone system by agonism of the angiotensin type 1 receptor. Its utility as a vasopressor and a catecholamine-sparing agent was demonstrated in the pivotal ATHOS-3 trial, and numerous post-hoc analyses have shown reduced mortality in certain subsets of the population. Methods: Consecutive adult patients at 5 centers who received Ang-2 from 2017-2020 were included in this multicenter, retrospective observational cohort study. Patient demographics, hemodynamics, and adverse events were collected. The primary outcomes of the study were the mean difference in MAP and norepinephrine (NEpi)-equivalent dose at hours 0 and 3 following initiation of Ang-2 therapy. Results: One hundred and sixty-two patients were included in this study. The primary outcomes of an increase in MAP (mean difference 9.3 mmHg, 95% CI 6.4-12.1, p < 0.001) and a reduction in NEpi equivalent dose (mean difference 0.16 µg/kg/min, 95% CI 0.10-0.22, p < 0.001) between hours 0 and 3 were statistically significant. The median time to reach a MAP ≥65 was 16 minutes (IQR 5-60 min). After stratifying patients by the NED dose and number of vasopressors administered prior to the initiation of Ang-2, those with a NED dose < 0.2 µg/kg/min, NED dose < 0.3 µg/kg/min, or those on ≤ 3 vasopressors had a significantly greater reduction in NED by hour 3 than those patients above these thresholds. Conclusion: Ang-2 is an effective vasopressor and reduces catecholamine dose significantly. Its effect is rapid, with target MAP obtained within 30 minutes in most patients. Given the critical importance of adequate blood pressure to organ perfusion, Ang-2 should be considered when target MAP cannot be achieved with conventional vasopressors. Ang-2 should be utilized early in the course of shock, before the NED dose exceeds 0.2-0.3 µg/kg/min and before the initiation of the fourth-line vasopressor.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Multicenter Observational Cohort Study of Angiotensin II in Shock

Smith

Newsome

Guo

et al. 2020

J Intensive Care Med

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“…In the ATHOS-3 protocol additional, pre-specified analyses were also planned [34][35][36]. First of all, differences in 28day mortality were analyzed and compared between two subgroups of ATHOS-3 patients.…”

Section: Efficacy and Safetymentioning

confidence: 99%

The Use of Angiotensin II for the Treatment of Post-cardiopulmonary Bypass Vasoplegia

Papazisi

Palmen

Danser

2020

Cardiovasc Drugs Ther

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Purpose Vasoplegia is a common complication after cardiac surgery and is related to the use of cardiopulmonary bypass (CPB). Despite its association with increased morbidity and mortality, no consensus exists in terms of its treatment. In December 2017, angiotensin II (AII) was approved by the Food and Drug Administration (FDA) for use in vasodilatory shock; however, except for the ATHOS-3 trial, its use in vasoplegic patients that underwent cardiac surgery on CPB has mainly been reported in case reports. Thus, the aim of this review is to collect all the clinically relevant data and describe the pharmacologic mechanism, efficacy, and safety of this novel pharmacologic agent for the treatment of refractory vasoplegia in this population. Methods Two independent reviewers performed a systematic search in PubMed, Embase, Web of Science, and Cochrane Library using relevant MeSH terms (Angiotensin II, Vasoplegia, Cardiopulmonary Bypass, Cardiac Surgical Procedures). Results The literature search yielded 820 unique articles. In total, 9 studies were included. Of those, 2 were randomized clinical trials (RCTs) and 6 were case reports and 1 was a retrospective cohort study. Conclusions AII appears to be a promising means of treatment for patients with post-operative vasoplegia. It is demonstrated to be effective in raising blood pressure, while no major adverse events have been reported. It remains uncertain whether this agent will be broadly available and whether it will be more advantageous in the clinical management of vasoplegia compared to other available vasopressors. For that reason, we should contain our eagerness and enthusiasm regarding its use until supplementary knowledge becomes available.

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“…Although this may highlight potential key populations for use, interpretation remains limited given the post hoc nature of the analysis and its statistical fragility (fragility index = 1). 40,41 Given the vast number of enzymes and organs involved within the RAAS, this therapy may be of higher consideration in certain populations. For example, patients with cirrhosis have decreased hepatic synthesis and, therefore, lower angiotensinogen levels.…”

Section: Future Directionsmentioning

confidence: 99%