Angiotensin II for Catecholamine Resistant Vasodilatory Shock in Patients with Acute Kidney Injury: A Post-Hoc Analysis of the ATHOS-3 Trial

ABSTRACT: Objective: The combination of catecholamine-resistant vasodilatory shock and acute kidney injury (AKI) is associated with high morbidity and mortality. The role of angiotensin II (ANGII) in this setting is unclear. Methods: We conducted a post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS) 3 trial which assessed the effect of Intravenous ANG II or placebo in patients with refractory vasodilatory shock in 75 intensive care units across nine countries in North America, Australasia, and Europe. We included patients with all stages AKI at initiation of ANG II or placebo and assessed 28-day mortality as primary outcome. We studied mean arterial pressure (MAP) response and days alive and free from renal replacement therapy (RRT) up to day 7 as secondary outcome. Results: Of 321 ATHOS-3 patients, 203 (63%) had AKI at randomization, with stage 3 AKI being dominant (67%). Median age was 63 years and median APACHE II score was 30. By day 28, overall, 118 (58%) of patients had died (53% with ANGII vs. 63% with placebo, hazard ratio = 0.75, 95% CI [0.52-1.08], P = 0.121). Among AKI stage 3 patients, however, ANGII was associated with significantly lower mortality (48% vs. 67%, hazard ratio = 0.57, 95% CI [0.36-0.91], P = 0.024). Additionally, in this subgroup, compared with placebo, patients receiving ANGII were more likely to achieve a MAP response (P < 0.001) and had more days alive and free from RRT (P < 0.001). Conclusions: Compared with placebo, in patients with catecholamine-resistant vasodilatory shock and stage 3 AKI, ANGII is associated with lower 28-day, greater likelihood of MAP response, and more days alive and free from RRT. These findings support the conduct of future ANGII trials in patients with stage 3 AKI.