Category: Breathing

Angioedma

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General Approach to Treatment

Icatibant for Angioedema

The Inside Scoop on Icatibant

Anand Swaminathan MD and Gentry Wilkerson MD   

 

Take Home Points

  • A previous phase II trial found the time to resolution of ACE-inhibitor induced angioedema was shorter after icatibant.
  • Another recent  randomized, controlled trial of icatibant compared to epinephrine, glucocorticoids and antihistamines found no benefit.
  • Our current understanding of the pathophysiology of ACE-inhibitor induced angioedema may be incorrect.

 

  • Wilkerson is a researcher in angioedema and icatibant. He has received research funding from Dyax, the makers of ecallantide and Shire, the makers of icatibant. This funding did not include salary support or speaking honoraria.

 

  • Bas, M et al. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. N Engl J Med. 2015 Jan 29;372(5):418-25. OPEN ACCESS LINK
    • This study found the time to resolution of ACE-inhibitor associated angioedema was significantly shorter with the use of icatibant compared to the combination therapy of glucocorticoid and antihistamine.

 

  • Glucocorticoid and antihistamines are not thought effective in ACE-inhibitor angioedema. Why not compare to fresh frozen plasma?
    • The authors state that using glucocorticoids and antihistamines are standard care in the sense that they are usual care. They do not imply that these are effective. They discuss the ineffectiveness of these medications in the introduction to the paper.
    • It would not be appropriate to study one unproven medication versus another unproven medication to see which is better. There are 13 case reports of FFP working in the treatment of ACE-inhibitor induced angioedema. These aren’t studies of effectiveness.

 

  • The natural course of angioedema is to get better; our role is to protect the patient until it does. While FFP contains the ACE enzyme which can break down accumulated bradykinin, it also contains high molecular weight kininogen which is a precursor to bradykinin. Theoretically, this could lead to increased bradykinin production.

 

  • We don’t have any proven treatment and we don’t know enough about the disease to design treatment. We think that the disease is due to bradykinin accumulation but we do not have proof.

Pathophysiology

 

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