If you blockade the angiotensin receptor system, you have a treatment for hypertension. If you agonize that same system, it logically follows you may have a corresponding treatment for hypotension. So, this is ATHOS-3, a phase 3 trial of synthetic human angiotensin II infusion in patients with catecholamine-resistant shock.
Roughly speaking, this is a trial evaluating the effectiveness of angiotensin for improving hemodynamic parameters in adult patients in vasodilatory shock – defined by the trialists as based on sufficient cardiac index, intravascular volume measurements, and persistent hypotension. Enrolled patients also needed to display ongoing hemodynamic derangement despite “high-dose vasopressors”. Exclusion criteria abound. The primary outcome was achievement of mean arterial pressure targets at 3 hours after initiation of angiotensin or placebo infusion.
Over the ~1.5 year study period, 404 patients were screened to ultimately initiate study protocol in 321. There’s little ambiguity with respect to the primary outcome – 69.9% of patients met MAP targets in the angiotensin cohort compared with 23.4% with placebo. Improvement in MAP led to corresponding downtitration of catchecholamine vasopressors in the intervention cohort. The intervention cohort displayed improvements in the cardiovascular SOFA, but no difference in overall SOFA at 48 hours. Mortality was quite high, regardless of group assignment, and no reliable difference was noted. Adverse events were common in each group with, again, no reliable differences detected.
This trial is mostly just interesting from a scientific awareness standpoint. The beneficial or harmful effects of angiotensin infusion are not established by these data. The enrolled population – approximately one patient every four months per site, on average – cannot be reliably generalized. As with any sponsored trial replete with conflict of interest among the authors – and particularly those with slow enrollment due to extensive exclusions – skepticism is particularly warranted. That said, this novel vasopressor clearly warrants additional study and comparative effectiveness evaluation.
“Angiotensin II for the Treatment of Vasodilatory Shock”