ACE Inhibitors and Angioedema
ABSTRACT & COMMENTARY
Source: Brown NJ, et al. Recurrent angiotensin-converting enzyme inhibitor-associated angioedema. JAMA 1997;278: 232-233.
Angiotensin-converting enzyme inhibitors (ACEIs) are associated with the development of angioedema. Brown and associates performed a retrospective cohort study of members of a state-sponsored medical insurance program who used ACEIs; previously, all of these patients had experienced an episode of angioedema. Brown et al identified 82 patients with an initially confirmed episode of angioedema related to ACEI userepresenting 1.6 cases per 1000 person-years. Among this group of patients, 16 recurrences of angioedema were noted in 13 patients. The rate of angioedema was statistically higher in continued users of an ACEI (18.7 per 100 patient-years) compared to patients who no longer used such medication (1.8 per 100 patient-years). Among those patients with a recurrence, critical care admission with intubation was required in 18% of patients with continued ACEI use. Medical record review further revealed that physicians frequently did not attribute the recurrent angioedema to ACEI despite multiple recurrences in several patients. In conclusion, Brown et al noted that continued use of an ACEI has an increased risk of angioedema that may be complicated by significant airway compromise.
COMMENT BY WILLIAM J. BRADY, MD
A previous study by Brown et al reported on 82 patients with angioedema which investigators thought to be secondary to ACEI use during 51,752 person-years of such treatmentrepresenting 1.6 cases per 1000 person-years.1 ACEI-related angioedema occurred three times as frequently in the population of patients using this medication compared to the general population. Further, they noted a markedly increased rate of angioedema in black Americans; other issues associated with an increased rate of development included: recent initiation of such therapy; use of lisinopril and enalapril; and recent hospitalization for any reason. Age, gender, ACEI dose, and the use of other vasoactive medications did not affect the rate of development. In the current study, demographic patterns among patients with recurrent angioedema were similar to cases with a single episode. From the initial study, 22% of patients with angioedema developed the condition within one month of treatment; the remaining patients (78%) manifested angioedema more than one month after ACEI therapy was started.1 According to the current study, recurrent angioedema developed, on average, 11 months after the initial exacerbation. Physicians frequently did not recognize the association between ACEI use and angioedema during the first episode of the complication; despite recurrent angioedema, physicians again often failed to make the causative association. The vast majority of patients with recurrence were managed initially in an emergency department.
This paper provides us with important information regarding the patient profile most at risk for angioedema as well as the concerning frequency of recurrence of this phenomenon. Both the initial episode and the recurrent event are associated with significant morbidity in the form of airway compromise. It also demonstrates that angioedema more often occurs with a delayed onset after the initiation of therapy. Lastly, the majority of patients with recurrence were initially managed in an emergency department and were misdiagnosed; we as emergency physicians must be aware of this entity and its characteristics.
Reference
1. Brown NJ, et al. Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. Clin Pharmacol Ther 1996;60:8-13.
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