Treatment of ACEI-related angioedema with icatibant: a case series

Abstract

No specific drugs are licensed for the treatment of ACE inhibitor (ACEI)-acquired angioedema (ACEI-AAE). Icatibant, an antagonist of the B2 receptor of bradykinin, is a potential treatment for this condition; however, its use in this setting is poorly documented. We report here clinical outcomes of 13 patients with ACEI-AAE treated with icatibant, in a real-life setting. Thirteen patients on ACEI seen in an Emergency Department (ED) with angioedema involving face, lips or the upper airways were analyzed. Angioedema due to known causes other than ACEI treatment was excluded. Initially, all patients received standard therapy (antihistamine, corticosteroids and epinephrine). Due to the lack of response and a worsening severity of symptoms, all patients received one subcutaneous injection of icatibant (30 mg/mL). Following icatibant treatment, all patients experienced improvement in the symptoms. The median time from onset of clinical symptoms to injection of icatibant was 3 h (IQR 2.5-5.5 h). Symptom relief was reported at 30 min (IQR 27.5-70 min). A complete resolution of symptoms was observed at 5 h (IQR 4-7 h). Ten patients had previously experienced angioedema attacks. The Median time to complete resolution of the previous attacks was higher (54 h; IQR 33-63 h), than after icatibant (p = 0.002) therapy. No patients required tracheal intubation or tracheotomy, and all patients were discharged within 24 h. No adverse events were reported. Before discharge, all patients were instructed to discontinue ACEI, and to take a different antihypertensive agent. This case series supports the efficacy of icatibant in improving symptoms of ACEI-AAE.

Off-Label Use of Agents for Management of Serious or Life-threatening Angiotensin Converting Enzyme Inhibitor–Induced Angioedema

“…38 Two case series comparing icatibant-treated patients with those previously treated with standard therapies found statistically significant improvements in time to complete symptom resolution. 46,47 A phase II randomized placebo-controlled trial of 27 patients with ACEI-IA presenting within 10 hours of symptom onset showed a statistically significant shorter time to complete edema resolution compared with standard therapy. 49 In clinical trials for HAE, almost all patients receiving icatibant experienced a self-limiting injection site reaction (97%), including erythema, edema, pain, and pruritus.…”

“…46 Two other case series noted no adverse events after icatibant administration. 47,48 Adverse events of redness, swelling, pain and itching and sensation of warmth were reported in patients receiving icatibant in the clinical trial; however, none were deemed serious. 49 There are no published studies on cost-effectiveness of the off-label use of agents approved for HAE in the management of ACEI-IA to justify their place in therapy and inclusion in ED inventory.…”

The Role of Mast Cells Mediators in Angioedema Without Wheals

“…It is administered subcutaneously (30-mg/3-ml syringes). Its effectiveness has been shown in multiple clinical trials for patients with types I and II HAE [47,48] and in case series in AAE-ACEi [49]. No serious adverse reactions have been reported.…”

Pharmacogenetics of angiotensin‐converting enzyme inhibitor‐induced angioedema

“…[64][65][66] The severity of ACEi-A varies; mild ACEi-A is more frequent, but symptoms can recur and potentially worsen overtime. 70 Rather, fresh frozen plasma, C1 esterase inhibitor or tranexamic acid had been found to be effective in several case series and are often utilized in real-life practice when first-line treatment fails. 23,30,69 A factor which often obscures or delays correct diagnosis is the variable time to onset.…”