Angiotensin II may improve vasopressors’ efficacy

WASHINGTON – Adding angiotensin II to available vasopressor therapies correlated with significantly improved arterial pressure in patients with catecholamine-resistant vasodilatory shock and less adverse effects, according to a study presented at the recent international conference of the American Thoracic Society.

In a double blind, controlled, phase III study, 70% of 163 patients given angiotensin II reached arterial pressure of at least 75 mm HG or improved by at least 10 mm Hg three hours later, compared with 23.4% of the 158 patients given a placebo (P less than .001).

Those in the angiotensin II group also saw a mean pressure increase of 12.5 mm Hg in the first 3 hours after initiating treatment, compared with 2.9 mm Hg in the placebo group (P less than .001), according to Ashish Khanna, MD, FCCP, of the Cleveland Clinic, and his fellow researchers (N Engl J Med. 2017 May 21. doi: 10.1056/NEJMoa1704154).

Current vasopressor therapies for vasodilatory patients are associated with dangerous side effects and a 30-day mortality rate of more than 50%, which is a major concern for patients who do not have many options to begin with, the researchers noted.

“Treatment options for patients with catecholamine-resistant vasodilatory shock are limited, and the treatments that are available are often associated with side effects,” said Dr. Khanna and his colleagues.

The researchers added the naturally occurring peptide hormone angiotensin II to vasodilatory patients’ treatment regimen in order to “more closely [mimic] natural physiologic responses to shock, which include increased secretion of catecholamines, vasopressin, and RAAS hormones.”

To test the efficacy of angiotensin II, researchers gathered patients with a median age of 64 years and a mean arterial pressure of 66.3 mm Hg.

Sepsis was the predominant cause of shock for 80.7% of the study’s participants.

Patients were injected with either 20 ng/kg of body weight per minute of angiotensin II or an equivalent dose of a placebo until mean arterial pressure reached 75 mm Hg. After 3 hours and 15 minutes of treatment, the dosages were adjusted to keep pressure between 65 and 75 mm Hg for the next 48 hours.

Among patients in the angiotensin II group, 67% of patients were able to decrease angiotensin II and vasopressor doses within 30 minutes of injection, according to researchers.

When researchers measured improvement using the cardiovascular Sequential Organ Failure Assessment, patients in the angiotensin II group saw an average decrease of 1.75 points, compared with 1.28 points in patients in the placebo group (P = .01) 48 hours after treatment.

The Sequential Organ Failure Assessment is scaled from 0-4, with higher scores indicating more severe organ failure.

When measuring for adverse affects, serious effects occurred in 60.7% of the angiotensin II patients, compared with in 67.1% of those in the placebo group.

At the 28-day mark, 75 angiotensin II patients (46.0%) died, compared with 85 patients (53.8%) of the placebo group.

This study was limited by the small sample size, “so the possibility of clinically important side effects attributable to angiotensin II therapy cannot be exuded,” the researches warned.

Also, the follow-up timeline of 28 days, may not have given researchers enough time to uncover the full extent of positive and negative long-term effects associated with angiotensin II.

This study was supported by La Jolla Pharmaceutical, from which multiple researchers reported receiving financial support in the form of personal fees and grants. Two of the researchers reported having patents related to administering angiotensin II and additional patents pending.

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