title: Effect of bradykinin receptor antagonism on ACE inhibitor-associated angioedema.
abstract: BACKGROUND
  The B2receptor antagonist icatibant is approved for treatment of attacks of hereditary angioedema. Icatibant has been reported to decrease time-to-resolution of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema in 1 study of European patients.
  
  
  OBJECTIVE
  We sought to test the hypothesis that a bradykinin B2receptor antagonist would shorten time-to-resolution from ACE inhibitor-associated angioedema.
  
  
  METHODS
  Patients with ACE inhibitor-associated angioedema (defined as swelling of lips, tongue, pharynx, or face during ACE inhibitor use and no swelling in the absence of ACE inhibitor use) were enrolled at Vanderbilt University Medical Center from October 2007 through September 2015 and at Massachusetts General Hospital in 2012. C1 inhibitor deficiency and patients with bowel edema only were excluded. Patients were randomized within 6 hours of presentation to subcutaneous icatibant 30 mg or placebo at 0 and 6 hours later. Patients assessed severity of swelling using a visual analog scale serially following study drug administration or until discharge.
  
  
  RESULTS
  Thirty-three patients were randomized and 31 received treatment, with 13 receiving icatibant and 18 receiving placebo. One patient randomized to icatibant did not complete the visual analog scale and was excluded from analyses. Two-thirds of patients were black and two-thirds were women. Time-to-resolution of symptoms was similar in placebo and icatibant treatment groups (P = .19 for the primary symptom and P > .16 for individual symptoms of face, lip, tongue, or eyelid swelling). Frequency of administration of H1 and H2 blockers, corticosteroids, and epinephrine was similar in the 2 treatment groups. Time-to-resolution of symptoms was similar in black and white patients.
  
  
  CONCLUSIONS
  This study does not support clinical efficacy of a bradykinin B2receptor antagonist in ACE inhibitor-associated angioedema.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: Brittany T
authors.initials: BT
authors.lastname: Straka
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Ramirez
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: James B
authors.initials: JB
authors.lastname: Byrd
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stone
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: Alencia
authors.initials: A
authors.lastname: Woodard-Grice
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: Hui
authors.initials: H
authors.lastname: Nian
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tenn.
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.affiliation: Massachussetts General Hospital, Boston, Mass.
authors.forename: Aleena
authors.initials: A
authors.lastname: Banerji
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn. Electronic address: Nancy.j.brown@vanderbilt.edu.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000799:Angioedema / Q000139:chemically induced* / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065094:Bradykinin B2 Receptor Antagonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D065094:Bradykinin B2 Receptor Antagonists; C065679:icatibant; D001920:Bradykinin
keywords: Angioedema; angiotensin-converting enzyme; bradykinin; icatibant; substance P