Recurrent angiotensin-converting enzyme inhibitor-associated angioedema

Context.-Angiotensin-converting enzyme (ACE) inhibitors are associated with an increased risk of angioedema, but the risk of recurrent angioedema if treatment is continued is not known. Objective.-To test the hypothesis that the association between ACE inhibitor use and angioedema may not be recognized and to determine characteristics of angioedema associated with continued use of ACE inhibitors. Design.-Retrospective cohort study. Setting.-Tennessee Medicaid program. Patients.-Medicaid enrollees aged 15 years or older who used an ACE inhibitor and had a first documented episode of angioedema between 1986 and 1992 were followed up for recurrent episodes through June 1993. Measurements and Main Results.-We previously identified 82 patients with a first confirmed diagnosis of angioedema during 51 752 person-years of ACE inhibitor use in this population (1.6 per 1000 person-years). Among these 82 patients, there were 16 outpatient recurrences of angioedema among 13 patients during 189 patient-years of follow-up (8.5 per 100 patient-years). The rate of angioedema was much higher in users of ACE inhibitors with continued exposure (18.7 per 100 patient-years) than in those whose use of the drug was discontinued (1.8 per 100 patient-years) (P=.001). Review of the medical records for patients taking ACE inhibitors who had recurrent angioedema revealed that physicians attributed angioedema to a number of causes not related to ACE inhibitor use, even after multiple recurrences. Conclusion.-Continuing use of ACE inhibitors in spite of angioedema results in a markedly increased rate of angioedema recurrence with serious morbidity.