Angioedema incidence in US veterans initiating angiotensin-converting enzyme inhibitors

Hypertension. 2008 Jun;51(6):1624-30. doi: 10.1161/HYPERTENSIONAHA.108.110270. Epub 2008 Apr 14.


Angioedema is a rare but potentially serious complication of angiotensin-converting enzyme inhibitor (ACE) use. We conducted a study to estimate incidence of ACE-related angioedema and explore its determinants in a large racially diverse patient population. We used linked medical and pharmacy records to identify all patients in the US Veterans Affairs Health Care System from April 1999 through December 2000 who received first prescriptions for antihypertensive medications. We studied 195 192 ACE initiators and 399 889 patients initiating other antihypertensive medications (OAH). New angioedema was identified by diagnosis codes using methods validated in a national sample of 869 angioedema cases with confirmation for over 95% of cases. Overall, 0.20% of ACE initiators developed angioedema while on the medication and the incidence rate was 1.97 (1.77 to 2.18) cases per 1000 person years. This compares with a rate of 0.51 (0.43 to 0.59) in OAH initiators and the adjusted relative risk estimate was 3.56 (2.82 to 4.44). Fifty five percent of cases occurred within 90 days of first ACE use but risk remained elevated with prolonged use, even beyond 1 year. We estimate that 58.3% of angioedema in patients starting antihypertensives was related to ACE. We also found that angioedema rates were nearly 4-fold higher in blacks, 50% higher in women, and 12% lower in those with diabetes. This study provides a reliable estimate of angioedema incidence associated with ACE use in a diverse nontrial patient population, confirming that the incidence is low, but finding substantial variation by race, sex, and diabetes status.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Angioedema / chemically induced*
  • Angioedema / epidemiology*
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / epidemiology*
  • Incidence
  • Male
  • Medical Records
  • Middle Aged
  • Regression Analysis
  • Risk Assessment
  • United States / epidemiology
  • United States Department of Veterans Affairs / statistics & numerical data
  • Veterans / statistics & numerical data*


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents