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Angioedema – Icatibant Rant

July 27, 2017

Spoon Feed
Icatibant did not improve outcome compared to placebo for ACE-I associated angioedema.

Icatibant rant… (well, not really…it just rhymed)
Angiotensin converting enzyme inhibitor (ACE-I) associated angioedema rarely causes laryngeal edema and airway compromise.  There are few effective treatment options. Icatibant is a selective bradykinin B2 receptor antagonist and is used in hereditary angioedema.  This RCT of 121 patients with ACE-I angioedema found no difference in time to safe discharge compared to placebo.  This meant, “the earliest time that difficulty breathing and difficulty swallowing were absent (rating of 0 out of 4), and voice change and tongue swelling were mild or absent (0 or 1).”  Most patients received conventional treatment with antihistamines, steroids, and epinephrine in both placebo and treatment groups. We can do some serious savings on healthcare costs by not pulling out this expensive drug for ACE-I angioedema.  The basics for treating angioedema apply.  If there are throat or voice complaints, visualize the airway with nasopharyngoscopy.  Secure the airway if there is any concern for progression.  Consider FFP as a treatment option, though the evidence for it isn’t great.  You can try epinephrine, steroids, and antihistamines as well, but they won’t help ACE-I associated disease.  Read this free full-text SAEM Consensus Guideline on Treatment of Angioedema…it’s good.

Another Spoonful
There’s a veritable cornucopia of FOAM on this paper.  Here are two of the best.

  • I found this thanks to PharmERToxGuy on Twitter – see his take.  I mean, really, who doesn’t regularly read the Journal of Allergy and Clinical Immunology Practice?
  • Anand Swaminathan does a play-by-play breakdown of the article on REBEL EM.

Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor-Induced Upper Airway Angioedema.  J Allergy Clin Immunol Pract. 2017 May 25. pii: S2213-2198(17)30172-1. doi: 10.1016/j.jaip.2017.03.003. [Epub ahead of print]

Peer reviewed by Thomas Davis.

2 thoughts on “Angioedema – Icatibant Rant

  • I think the blanket statement that we shouldn’t use the drugs targeting bradykinin-induced angioedema when someone is taking an ACEi based on the available data is problematic. A not insignificant number of patients taking an ACE will manifest angioedema because of underlying hereditary or acquired C1 esterase deficiency and for this population, icatibant or berinert could be life-saving and/or intubation-sparing. Unfortunately, we don’t have rapid and efficient means to identify this population. If we could stave off intubation and the inherent risks associated with both placing the tube as well as time spent on a ventilator (not to mention the cost), I say give the med or at the very least keep it in your arsenal.

    With regard to the SAEM consensus guidelines, the following statement is problematic, "In patients with idiopathic angioedema unresponsive to H1-antagonists, epinephrine and corticosteroids, without a family history of angioedema, in the absence of direct evidence for bradykinin as the primary mediator of swelling, it would be premature to recommend the use of therapies approved for HAE." Direct evidence? How are we to know? POC C4 level?

    Finally, developing angioedema while on an ACEi doesn’t guarantee that it isn’t a histamine-mediated event, in which case epi, steroids, H1 blocker would be of benefit. How do we know this didn’t influence the outcome of this study since most received these meds?

    • Jeremy Greenberg
    • Sorry for the delayed reply. I certainly miss seeing you, friend. These comments really make me think, especially the concept that we don’t know when they arrive whether it may have some response to epinephrine, antihistamines, etc. And the cost and burden of being on a ventilator certainly should factor into the analysis when considering the benefit of these drugs. As usual, interaction with you makes me a better doctor. Keep it coming.

What are your thoughts?