Clinical Review NOVEL THERAPIES FOR ANGIOTENSIN-CONVERTING ENZYME INHIBITOR–INDUCED ANGIOEDEMA: A SYSTEMATIC REVIEW OF CURRENT EVIDENCE Heidi M. Riha, PHARMD, BCPS,* Bryant B. Summers, PHARMD, BCPS,† Jessica V. Rivera, PHARMD, BCPS,‡ and Megan A. Van Berkel, PHARMD, BCPS, BCCCP* *Department of Pharmacy, Erlanger Health System, Chattanooga, Tennessee, †Department of Pharmacy, Henry Ford Hospital, Detroit, Michigan, and ‡Department of Pharmacy, University of Alabama at Birmingham Hospital, Birmingham, Alabama Reprint Address: Megan A. Van Berkel, PHARMD, BCPS, BCCCP, Department of Pharmacy, Erlanger Health System, 975 E. 3rd St. Chattanooga, TN, 37403 , Abstract—Background: Angiotensin-converting enzyme inhibitor (ACEI)–induced angioedema can occur at any point during therapy and, when severe, can require mechan- ical ventilation. Standard agents for anaphylactic reactions have limited efficacy for bradykinin-mediated angioedema and, therefore, agents approved for hereditary angioedema are increasingly prescribed for these patients. Objective of the Review: This systematic review critically evaluates evi- dence describing the off-label use of fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), comple- ment 1 esterase inhibitor (C1-INH), icatibant, and ecallan- tide for treatment of ACEI-induced angioedema. Discussion: A PubMed search was conducted and articles were cross-referenced for additional citations. All full-text clinical trials, case series, and case reports published in the English language describing pharmacologic treatment of ACEI-induced angioedema were included. Thirty-seven publications detailing FFP, PCC, and regimens approved for hereditary angioedema, including icatibant, ecallantide, and C1-INH, are reviewed extensively. Conclusions: While findings of decreased time to symptom resolution or a cessation in symptom progression have been reported with each of these therapies, additional data showing clin- ically relevant implications, such as reduced intensive care unit length of stay or avoidance of mechanical ventilation, are warranted, especially when taking cost into consider- ation. FFP has limited evidence demonstrating a benefit for treatment of ACEI-induced angioedema without consistent dosing strategies. However, given its wide avail- ability and low potential for adverse reactions, FFP ther- apy may be reasonable. Of the novel agents traditionally used for hereditary angioedema, icatibant has the highest level of evidence and has been reported to be successful in limiting the progression of angioedema. Ó 2017 Elsev- ier Inc. All rights reserved. , Keywords—angiotensin converting enzyme inhibitor; angioedema; C1-esterase inhibitor; ecallantide; emergency medicine; icatibant; intubation INTRODUCTION Angioedema is characterized by sudden, self-limited swelling of the dermis, subcutaneous, and submucosal tissues (1,2). Approximately 15–25% of the general population will experience angioedema, with women affected more frequently (2,3). While different forms of angioedema exist, all exhibit nonpitting edema as a result of increased permeability of post-capillary venules (3). Most commonly, swelling is noted in the periorbital area, lips, tongue, larynx, and pharynx (1,2). However, other areas of involvement may include the extremities, gastrointestinal tract, and genitalia (1). Although rare, of most concern is airway swelling and compromise, RECEIVED: 1 February 2017; FINAL SUBMISSION RECEIVED: 15 May 2017; ACCEPTED: 30 May 2017 1 The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–18, 2017 Ó 2017 Elsevier Inc. All rights reserved. 0736-4679/$ - see front matter http://dx.doi.org/10.1016/j.jemermed.2017.05.037