Novel Therapies for Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Systematic Review
Standard therapy for angiotensin-converting enzyme inhibitor (ACEI) – induced angioedema includes agents for anaphylaxis including steroids and histamine blockade, however, little evidence exists to support this practice. Targeted therapies exist for hereditary angioedema and are at times used off-label for its ACEI counterpart yet are often prohibitively expensive. As these therapies become more widely available, the study’s authors conducted a systematic review of available evidence for targeted therapies and their use in ACEI-induced angioedema. The reviewed evidence for each therapy is summarized below:
9 studies, 16 patients. Dosing varied across trials, however, 13/16 patients did not experience progression of symptoms or had resolution of symptoms after receiving FFP
1 case report with symptomatic improvement within 20 minutes, resolution after 8 hours with administration of 1500 U of PCC.
C1 Esterase Inhibitor
2 prospective trials, 83 patients. Patients who received 20 IU/kg of C1-INH within 6 hours of onset had faster resolution of their symptoms. Several additional case reports demonstrated variable outcomes ranging from requirement for additional therapeutic interventions to symptomatic resolution. Doses varied widely across studies.
Randomized double blind study of 83 patients which excluded patients with imminent airway compromise. Ultimately no difference between groups. Additional studies showed a non-statistically significant increase in discharges in ACEI-inhibitor induced angioedema with treatment with ecallantide.
Multiple case studies, including 1 case study where icantibant prevented intubation. An additional study of 13 patients showed a faster time to symptom resolution
The Bottom Line
Data in support of these therapies is very heterogenous. While some therapies seem to improve symptom resolution, it is difficult to draw broad conclusions in the face of significant heterogeneity of both primary outcomes and drug administration. Many of these case reports exclude patients with concern for or with imminent airway compromise, arguably the outcome most concerning to any emergency physician when caring for a patient with angioedema. There is currently little to no evidence to support that these therapies prevent intubation or ICU admission in patients with ACEI-induced angioedema and concern for airway involvement. The benefit of marginally faster symptomatic resolution and subsequent small decrease in ED LOS alone does not seem to outweigh the prohibitive cost of these targeted therapies at this time.