Epidemiology of ACE Inhibitor Angioedema Utilizing a Large Electronic Health Record

J Allergy Clin Immunol Pract. 2017 May-Jun;5(3):744-749. doi: 10.1016/j.jaip.2017.02.018. Epub 2017 Apr 1.


Background: Angiotensin-converting enzyme inhibitors (ACEIs) are a common cause of drug-induced angioedema in the United States. Most epidemiologic ACEI angioedema data are from large multicenter clinical trials.

Objective: The objective of this study was to identify the incidence of and risk factors for ACEI angioedema using a large integrated electronic health record (EHR).

Methods: We conducted a retrospective cohort study of all ACEI prescriptions in the outpatient setting of a large academic center between January 1, 2000, and September 30, 2008. We determined frequency, timing, and risk factors for ACEI angioedema within 5 years of prescription. All data were derived from EHR sources, with angioedema defined by EHR reactions of angioedema, swelling, edema, or lip, eye, face, tongue, throat or mouth swelling.

Results: Among 134,945 patients prescribed an ACEI, 0.7% (n = 888) developed angioedema during the subsequent 5 years. Sex was similar but patients who developed ACEI angioedema were younger (61.5 vs 62.7 years, P = .007). Patients with ACEI angioedema were more likely to have a history of nonsteroidal anti-inflammatory drug allergy compared with patients who did not develop angioedema (7.1% vs 4.2%, P < .001). We identified a 0.07% incidence of ACEI angioedema within 1 month of prescription and a 0.23% incidence during the first year. Incidence of angioedema was relatively constant annually over the subsequent 4 years (0.10% to 0.12%).

Conclusions: The incidence of ACEI angioedema within a large EHR is consistent with large clinical trial data. We observed a persistent and relatively constant annual risk; however, angioedema risk factors and underlying genetic and pathophysiological mechanisms require further study.

Keywords: Angioedema; Angiotensin-converting enzyme; Drug allergy; Drug hypersensitivity; Electronic health record; Epidemiology.

MeSH terms

  • Age Factors
  • Allergens / immunology*
  • Angioedema / epidemiology*
  • Angiotensin-Converting Enzyme Inhibitors / immunology*
  • Anti-Inflammatory Agents, Non-Steroidal / immunology
  • Cohort Studies
  • Drug Hypersensitivity / epidemiology*
  • Electronic Health Records / statistics & numerical data*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk
  • United States / epidemiology


  • Allergens
  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Inflammatory Agents, Non-Steroidal