Treatment With Angiotensin II Is Associated With Rapid Blood Pressure Response and Vasopressor Sparing in Patients With Vasoplegia After Cardiac Surgery: A Post-Hoc Analysis of Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) Study

Abstract

Objective: The present study investigated outcomes in patients with vasoplegia after cardiac surgery treated with angiotensin II plus standard-ofcare vasopressors. Vasoplegia is a common complication in cardiac surgery with cardiopulmonary bypass and is associated with significant morbidity and mortality. Approximately 250,000 cardiac surgeries with cardiopulmonary bypass are performed in the United States annually, with vasoplegia occurring in 20%to-27% of patients. Design: Post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. Setting: Multicenter, multinational study. Participants: Sixteen patients with vasoplegia after cardiac surgery with cardiopulmonary bypass were enrolled. Interventions: Angiotensin II plus standard-of-care vasopressors (n = 9) compared with placebo plus standard-of-care vasopressors (n = 7). Measurements and Main Results: The primary endpoint was mean arterial pressure response (mean arterial pressure 75 mmHg or an increase from baseline of 10 mmHg at hour 3 without an increase in the dose of standard-of-care vasopressors). Vasopressor sparing and safety also were assessed. Mean arterial pressure response was achieved in 8 (88.9%) patients in the angiotensin II group compared with 0 (0%) patients in the placebo group (p = 0.0021). At hour 12, the median standard-of-care vasopressor dose had decreased from baseline by 76.5% in the angiotensin II group compared with an increase of 7.8% in the placebo group (p = 0.0013). No venous or arterial thrombotic events were reported.

Commentary: Is angiotensin II a game changer for vasoplegia after cardiac surgery, or is the jury still out?

“…Although relatively few patients in the ATHOS-3 trial had undergone cardiac surgery (4.7%; 16 of 344), this was examined in detail in a post hoc analysis. 6 In that report, 89% of the cardiac surgery cohort reached the target mean arterial pressure. In addition, the overall ATHOS-3 Ang-II cohort had a higher rate of venous thromboembolism (VTE) than the standard of care group (13% vs 5%) but a similar rate of clinically significant VTEs (2% vs 0%).…”

Commentary: Angiotensin II: Expanding the rescue options for vasoplegia

“…5 This vasopressor-sparing effect may minimize the ischemic risk by supporting a more balanced restoration of vascular tome. [7][8][9] Although this report expands the therapeutic armamentarium for vasoplegia, it also highlights some important caveats with this vasopressor. [5][6][7][8][9] The first caveat is that we know very little about adverse events associated with angiotensin II, owing to the limited evidence base.…”

Underutilized Fuel: Angiotensin II for Vasoplegia in the Heart Failure Patient Population

“…We would like to congratulate the authors of their post-hoc analysis of Angiotensin II (ANG-II) for the treatment of vasoplegia in patients following cardiac surgery. 1 The study found that patients with vasoplegia after cardiac surgery with cardiopulmonary bypass rapidly responded to ANG-II with swift blood pressure response and rapid down titration of standard of care vasopressors with no reported thrombosis. 1 Early recognition and treatment of vasoplegia improves survival and reduces risks of major adverse events.…”

“…1 The study found that patients with vasoplegia after cardiac surgery with cardiopulmonary bypass rapidly responded to ANG-II with swift blood pressure response and rapid down titration of standard of care vasopressors with no reported thrombosis. 1 Early recognition and treatment of vasoplegia improves survival and reduces risks of major adverse events. 2 However, in patients with heart failure and severe vasoplegia, treatment with ANG-II is not widely utilized despite the data demonstrating the efficacy of the drug.…”

“…Furthermore, the median pressor dose decreased from baseline by 76.5% in the ANG-II group compared with an increase of 7.8% in the placebo group (p = < 0.05). 1 This makes ANG-II very favorable to the cardiac critical care patient. Given the rapid improvement in the hemodynamic profile upon initiation, one of the advantages of ANG-II may be the beneficial reduction in myocardial oxygen demand following withdrawal of other pressors.…”