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

Kealy R Ham,Laurence W Busse,George F Tidmarsh,Michael T Mccurdy,Raphael Favory,Marlies Ostermann,Ashish K Khanna,Lakhmir S Chawla,Stefan N Chock,Feng Zeng,Michelle N Gong,David W Boldt

doi:10.1186/s13613-019-0536-5

Abstract

BackgroundEarly 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.ResultsThe 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.ConclusionsThis 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.

Highlights

Clinical data showed that some patients with vasodilatory shock are responsive to low doses of angiotensin Acute Physiology and Chronic Health Evaluation II (II)
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 mean arterial pressure (MAP) versus the > 5 ng kg−1 min−1 subgroup (84/163)
Day 28 survival was 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% confidence interval (CI) 0.28–0.72], P = 0.0007); multivariate analyses supported the survival benefit in patients with lower angiotensin II levels

Summary

Introduction

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). Vasopressin [3], is effective in some patients and may allow the lowering of catecholamine dose, but it has not been shown to improve survival [3]. Fewer than 50% of patients in shock generate a blood pressure response to treatment with vasopressin [11], and

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