Firazyr of Limited Help with Angioedema Caused by ACE Inhibitors, Pooled Trial Data Suggest

Firazyr (icatibant acetate) does not appear to be superior to placebo or symptomatic therapies in treating attacks of angioedema (swelling) caused by angiotensin-converting enzyme (ACE) inhibitors, a pooled analysis of three clinical studies shows.

In all trials combined, injections of Firazyr considerably shortened mean time to symptom resolution, but this difference was not statistically significant.

These findings were reported in the study “Effect of icatibant on angiotensin‐converting enzyme inhibitor‐induced angioedema: A meta‐analysis of randomized controlled trials,” published in the Journal of Clinical Pharmacy and Therapeutics.

Angioedema, characterized by acute attacks of swelling (edema) in the deep layers of the skin or mucous membranes, can occur anywhere but is commonly found in the face or limbs. The swelling results from fluid leaking from small blood vessels into tissues, either as a result of a genetic condition (called hereditary angioedema or HAE), or a variety of triggers.

Some people develop it as non-allergic reaction to treatment with angiotensin-converting enzyme (ACE) inhibitors, medicines that lower blood pressure by making blood vessels relax and dilate (widen). ACE inhibitors are used mainly to treat certain heart and kidney conditions.

These inhibitors also increase the amount of bradykinin, another substance that makes blood vessels dilate and become more permeable. For this reason, a small proportion of people taking ACE inhibitors will have peaks of bradykinin in the body, leading to excess fluid leakage into tissues and episodic attacks of angioedema.

Angioedema is a potentially life-threatening condition should swelling affect the airways. “There are no specific treatment guidelines for ACEI‐induced AE [ACE inhibitor-induced angioedema], and its management includes discontinuation of the causative drug, airway monitoring and symptomatic treatment with drugs such as antihistamines, corticosteroids and epinephrine,” the researchers wrote.

People with ACE inhibitor-induced angioedema, however, often do not respond to these medications.

Some recent studies suggest that Firazyr — approved  for hereditary angioedema (HAE) — might also help those with ACEI-induced angioedema; others studies have shown no promising effect.

Firazyr, marketed by Takeda, is an FDA-approved medicine for treating symptoms of acute attacks of HAE in adults ages 18 or older. The European Union also allows its use for adolescents and children starting at 2 years old. It is given as subcutaneous, or under the skin, injections.

Firazyr blocks the activity of bradykinin by binding to its receptor in cells. The usual dose for adults is an injection of 30 mg, with a second dose allowed after six hours and up to a maximum of three injections per day.

To gather evidence for Firazyr’s use in people with ACE inhibitor-induced angioedema, researchers did a pooled analysis, or meta-analysis, of three randomized controlled trials involving 179 patients who had been treated with the medicine versus a placebo or conventional therapy.

Data showed that those given Firazyr tended to achieve complete resolution of symptoms earlier — a mean of 7.7 hours less — compared to placebo or conventional treatments.

However, this difference was not statistically significant. Researchers say this may be so due to the wide range of median times for complete resolution among patients. That range was four to 25 hours.

No differences were found between groups in terms of adverse events, whether treatment-related or not, except for reactions at the site of injection.

Erythema (skin redness) was the most common injection site reaction, and more than twice as common in the Firazyr group than in the control group.

Although this analysis suggests that Firazyr does not benefit patients with ACEI-induced anioedema over standard treatment, its researchers said their study had limited power for detecting the medicine’s superiority because only a small number of trials are available, and their design varied considerably (e.g., in terms of outcome measures, control groups).

“Additional [randomized clinical trials] are required to assess the efficacy of icatibant therapy for ACEI‐induced AE before it can be recommended for use in clinical practice,” the researchers concluded.