Angioedema Incidence in US Veterans Initiating Angiotensin-Converting Enzyme Inhibitors

Abstract

Abstract-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.

Orolingual angioedema after thrombolysis is not associated with insular cortex ischemia on pre-thrombolysis CT

“…Other case control-studies found a higher frequency of OA in women [3,5] and, in our study, female sex was an independent risk factor for OA, which is in accordance to a large cohort study of medication-related angioedema incidence [9]. The reason for this sex difference is not clear, but may include the influence of sex hormones on the regulation of inflammation and an increased T h 2 immune response in women [10], which is further supported by the female predominance of chronic urticaria, a condition with a pathophysiology closely linked to acquired angioedema [11].…”

Angiotensin-Converting Enzyme Inhibitors and Angioedema

“…Still, it is likely that even more events would have occurred had the study been extended to the same length as other experiences. 2,7 Analysis of the factors that predicted angioedema events in OCTAVE confirmed that black patients were almost 3 times as likely as others to experience an episode. Previous histories indicative of allergic reactions, including rashes during treatment with other types of drugs, or episodes of seasonal allergy, were also predictive of angioedema.…”

“…2 By studying all patients started on ACE inhibitors during a particular time period in the Veterans Affairs medical system, these investigators were able to count angioedema outcomes in a cohort numbering almost 200 000. This type of observation has the virtue of being carried out entirely within a closed healthcare system, so that all individuals presenting with angioedema-either as outpatients or inpatients-would have retrievable documentation of their diagnosis.…”

“…The article by Miller et al in this issue of Hypertension represents a careful effort to estimate the frequency of this event in contemporary clinical practice. 2 One of the chief attributes of the ACE inhibitors has been their overall tolerability. By far the most commonly encountered complaint with these agents is a dry, nonproductive cough.…”

“…Sadly, this reassuring statement has not turned out to be true. Reports during the past 3 years, 7,8 including that of Miller et al, 2 have emphasized that although a relatively high proportion of angioedema episodes occur during the early part of treatment, these serious events can be observed after months or even years of ACE inhibitor therapy. In fact, in a large clinical survey by Zingale et al the average ACE inhibitor exposure before the occurrence of angioedema was a full 12 months; remarkably, it took an additional 12 months from the occurrence of the angioedema until the ACE inhibitor therapy was discontinued.…”