Angiotensin II Effectively Treats Vasodilatory Shock, Researchers Say

A new study published by The New England Journal of Medicine shows promising results for angiotensin II for treatment-resistant vasodilatory shock.

Researchers showed that the intervention increased blood pressure in patients with the condition who previously had not responded to other vasopressors — patients who typically exhibit high mortality rates.

In the ATHOS-3 trial, researchers worked with 321 patients, 163 of which received angiotensin II and 158 of which received a placebo. More patients in the study group (114) reached the primary endpoint than the placebo group (37). The study had a confidence interval of 95% and a P value of less than 0.001.

Researchers checked patients’ blood pressure three hours into the intervention and found that 69% in the test group had reached the target blood pressure. This compares to 23.4% in the control group.

The team also looked at mean improvement of the cardiovascular Sequential Organ Failure Assessment (SOFA) scores after 48 hours. SOFA rates patients on a 0 to 4 scale. Patients in the group that received angiotensin had better mean SOFA rates (-1.75) than the placebo group (-1.28) after 48 hours.

“In this multinational, double-blind, randomized, controlled trial involving patients with vasodilatory shock who were receiving high doses of conventional vasopressors, the percentage of patients who met the primary endpoint with respect to mean arterial pressure at 3 hours was significantly greater in the angiotensin II group than in the placebo group,” the study concludes.

For the purpose of the study, researchers looked at patients from 75 intensive care units from 9 countries in North America, Australia, Asia and Europe. The study took place from May 2015 through January 2017.

Researchers also highlighted the relative safety of angiotensin II, as compared to traditional treatment options. In the angiotensin II group, 60.7% of patients experienced an adverse event, compared to 67.1 in the placebo group. Forty-six percent of the angiotensin II group died by the 28^th day of the trial while 54% of the patients died by the 28^th day in the control group.

Compared to earlier interventions, the study authors say that previous therapies — such as glucocorticoids, high-volume hemofiltration, methylene blue and vasopressins – are associated with adverse events and/or higher 28-day mortality.

“In contrast,” the authors wrote, “in our study, angiotensin II was not associated with higher mortality or a greater frequency of cardiovascular and other adverse events than was placebo.”

The study also notes that those treated with angiotensin II needed fewer catecholamines than patients in the placebo group.

Angiotensin II is under development by La Jolla Pharmaceutical Company, which sponsored the trial. In a news release issued by the company, researcher Dr. Rinnaldo Bellomo, M.D., professor of intensive care medicine at University of Melbourne and Director of Intensive Care Research at Austin Health, highlighted the significance of the new therapy.

“There is a major need for new treatment options for critically ill patients who do not adequately respond to available vasopressors,” he said. “If approved, angiotensin II, in combination with other vasopressors, may allow clinicians to leverage all three major physiologic symptoms that regulate blood pressure.”