Icatibant treatment effect in ACE inhibitor-induced angioedema not shown in randomized study

Published online: May 25, 2017

Angiotensin converting enzyme (ACE) inhibitors prevent breakdown of bradykinin, a substance in the body that causes blood vessels to enlarge and blood pressure to fall. These commonly used medications are a first-line option for treating high blood pressure, heart failure, and diabetic kidney disease. However, their use is associated with a risk of acute angioedema—a rare, potentially life-threatening condition characterized by rapid swelling in various regions throughout the body, thought to be caused by an overload of bradykinin. Angioedema attacks involving the throat are particularly dangerous because the swelling can block the airway, making it impossible to breathe. Unfortunately, to date, no treatments for angioedema caused by ACE inhibitors have been reliably effective; research in this important area continues.

Icatibant, a bradykinin B2 receptor blocker, has shown efficacy in treating symptoms of hereditary angioedema, a rare genetic disease that causes similar swelling; the usefulness of this medication in treating other types of angioedema continues to be studied. In a recent issue of The Journal of Allergy and Clinical Immunology: In Practice, Sinert and colleagues present results from a clinical study evaluating the efficacy of icatibant versus placebo in adults receiving ACE inhibitors who arrived at the emergency room within 12 hours from the time of angioedema  onset, and whose attack was at least moderately severe. Patients with angioedema attacks unrelated to use of ACE inhibitors were not entered into the study.

A total of 121 patients with angioedema likely caused by ACE inhibitors were randomly assigned to receive icatibant or placebo; most (>90%) had received anti-allergy medications before the study drug. Results showed no noticeable differences between treatment groups in the time to meet discharge criteria after the study drug was given. Similarly, no major differences were found in time to onset of symptom relief or other efficacy measures.

The negative findings were surprising, given the suggested role of bradykinin in angioedema caused by ACE inhibitors, and the results of a key previous, smaller study in which icatibant was effective for angioedema caused by ACE inhibitors.1 Several things may have contributed to the difference in results, including a longer time in the current study from the start of swelling to the time the study drug was given. It is also possible that some patients in the current study had angioedema unrelated to use of ACE inhibitors, since most patients had received anti-allergy medications and those in the placebo group recovered from the angioedema attack faster than expected. However, it is presently not possible to determine the exact cause of angioedema when a patient presents with related symptoms in the emergency room, and the current study used strict criteria when enrolling patients, which reduced the chance of this occurring. In addition, how quickly patients recover from angioedema attacks caused by ACE inhibitors, and how well they respond to anti-allergy medications, varies across studies. Taken together, results from the current study suggest that bradykinin and B2 receptor interaction in angioedema caused by ACE inhibitors may not be as important as previously thought and emphasize the need for further research.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

1. Bas M, et al. N Engl J Med 2015; 372:418-425.

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