Multicenter study of patients with angiotensin-converting enzyme inhibitor-induced angioedema who present to the emergency department

doi:10.1016/S1081-1206(10)60594-7

Annals of Allergy, Asthma & Immunology

Volume 100, Issue 4, April 2008, Pages 327-332

https://doi.org/10.1016/S1081-1206(10)60594-7 Get rights and content

Background

Recent data are lacking about the number of patients with angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema who present to the emergency department (ED). Current management of the condition and clinical outcomes also are not known.

Objective

To describe the clinical epidemiology of ACEI-induced angioedema in patients who present to the ED.

Methods

We performed a medical record review of ACEI-induced angioedema in patients who presented to 5 EDs in the Emergency Medicine Network. A structured data abstraction form was used to collect each patient's demographic factors, medical history, and details about the angioedema that prompted the ED visit. The medical record review also focused on treatment provided in the ED and subsequent need for hospitalization.

Results

We identified a total of 220 patients with ACEI-induced angioedema. The frequency of ACEI-induced angioedema among all patients with angioedema who presented to the ED was 30% (95% confidence interval, 26%-34%). The annual rate of visits for ACEI-induced angioedema was 0.7 per 10,000 ED visits. The most frequent presenting signs were shortness of breath, lip and tongue swelling, and laryngeal edema. Most patients (58%) were sent home directly from the ED, whereas 12% were regular inpatient admissions, 11% were admitted to the intensive care unit, and 18% were admitted under observation status (<24 hours). Pharyngeal swelling and respiratory distress were independent predictors of hospital admission and longer length of stay.

Conclusion

ACEI-induced angioedema accounted for almost one-third of angioedema treated in the ED, although it remains a rare ED presentation. A subgroup of these patients still needs inpatient hospitalization for management of upper airway angioedema.

Section snippets

INTRODUCTION

Angioedema is a life-threatening adverse event associated with angiotensin-converting enzyme inhibitor (ACEI) therapy. The number of patients taking ACEIs continues to rise, leading to increasing rates of angioedema.¹ In 2001, there were 35 million to 40 million prescriptions written for ACEIs worldwide,² and in 2007, ACEIs remain the most frequent class of medications prescribed for the treatment of hypertension.³ Angioedema occurs in approximately 0.1% to 2.2% of patients treated with ACEIs,4

MATERIALS AND METHODS

This study is a retrospective medical record review of angioedema in patients who presented to 5 EDs in the Emergency Medicine Network (www.emnet-usa.org). Each site obtained approval from their institutional review board and was asked to review all cases of angioedema in patients who presented to the ED between 2003 and 2005. The target sample size was 1,000 patients across the 5 sites. Prior studies from a decade ago suggested that approximately 30%10, 13, 14 of these 1,000 patients will have

Frequency of ACEI-Induced Angioedema

Among the 5 participating sites, we identified a total of 586 patients who presented to the ED with angioedema between 2003 and 2005. Among these 586 patients with angioedema, 175 patients (30% [95% CI, 26%-34%]) were found to have ACEI-induced angioedema. The percentage of angioedema cases associated with ACEIs was consistent across years (Fig 1).

Three sites did not reach the predetermined goal of 60 ACEI-induced angioedema cases per site and therefore gathered data from other years (ie, 1998

DISCUSSION

Our study found an overall frequency of 30% of ACEI-induced angioedema among all patients with angioedema who presented to the ED. ACEI-induced angioedema accounts for almost one-third of angioedema treated in the ED. This percentage is similar to data from studies completed more than a decade ago, which reported values of approximately 30% to 38%.10, 13, 14 Although there was slight variability among the 5 different sites in this study, ACEI-induced angioedema is a rare ED presentation (0.7

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Angiotensin converting enzyme inhibitors (ACE-Is) prevent the breakdown of bradykinin and can lead to life threatening angioedema. Tranexamic acid is an antifibrinolytic that inhibits formation of precursors involved in bradykinin synthesis and, in case reports, has been described as a potential treatment for ACE-I angioedema.
This retrospective study included patients who presented to the emergency department (ED) from January 2018 to August 2021 with angioedema while taking an ACE-I. Patients who received tranexamic acid (treatment group) were compared with patients who did not receive tranexamic acid (control group). Primary outcome was length of stay (LOS). Secondary outcomes evaluated included ICU admissions, intubations, and safety events.
A total of 262 patients were included in this study (73 treatment; 189 control). Overall, the median ED LOS was longer in the treatment group than controls (20.9 h vs 4.8 h, p < 0.001). ICU admission rates were higher in the treatment group (45% vs 16%, p < 0.001). More patients were intubated in the treatment group (12% vs 3%, p = 0.018). No difference was seen between the treatment group and the controls for return within 7 days, complications related to thrombosis, and death. In patients presenting with severe angioedema symptoms who were admitted to the hospital, median LOS was not different between the two groups (58.7 h vs 55.7 h, p = 0.61).
Patients who received tranexamic acid had increased ED LOS, rates of ICU admission, and need for intubation. This finding may be related to the severity of presentation. Administration of tranexamic acid appears safe to use in ACE-I angioedema. Prospective randomized controlled studies should be considered to determine whether tranexamic acid is an effective treatment for ACE-I angioedema.
Meta-analysis of ACE inhibitor–induced angioedema identifies novel risk locus
2024, Journal of Allergy and Clinical Immunology
Angioedema is a rare but potentially life-threatening adverse drug reaction in patients receiving angiotensin-converting enzyme inhibitors (ACEis). Research suggests that susceptibility to ACEi-induced angioedema (ACEi-AE) involves both genetic and nongenetic risk factors. Genome- and exome-wide studies of ACEi-AE have identified the first genetic risk loci. However, understanding of the underlying pathophysiology remains limited.
We sought to identify further genetic factors of ACEi-AE to eventually gain a deeper understanding of its pathophysiology.
By combining data from 8 cohorts, a genome-wide association study meta-analysis was performed in more than 1000 European patients with ACEi-AE. Secondary bioinformatic analyses were conducted to fine-map associated loci, identify relevant genes and pathways, and assess the genetic overlap between ACEi-AE and other traits. Finally, an exploratory cross-ancestry analysis was performed to assess shared genetic factors in European and African-American patients with ACEi-AE.
Three genome-wide significant risk loci were identified. One of these, located on chromosome 20q11.22, has not been implicated previously in ACEi-AE. Integrative secondary analyses highlighted previously reported genes (BDKRB2 [bradykinin receptor B2] and F5 [coagulation factor 5]) as well as biologically plausible novel candidate genes (PROCR [protein C receptor] and EDEM2 [endoplasmic reticulum degradation enhancing alpha-mannosidase like protein 2]). Lead variants at the risk loci were found with similar effect sizes and directions in an African-American cohort.
The present results contributed to a deeper understanding of the pathophysiology of ACEi-AE by (1) providing further evidence for the involvement of bradykinin signaling and coagulation pathways and (2) suggesting, for the first time, the involvement of the fibrinolysis pathway in this adverse drug reaction. An exploratory cross-ancestry comparison implicated the relevance of the associated risk loci across diverse ancestries.
Ultrasound airway assessment of angioedema in the emergency department
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Differences in Hypersensitivity Reactions to Iodinated Contrast Media: Analysis of the US Food and Drug Administration Adverse Event Reporting System Database
2023, Journal of Allergy and Clinical Immunology: In Practice
A comparative hypersensitivity risk profile of frequently used iodinated contrast media (ICM) may be required for their safer use.
To explore the association between hypersensitivity reactions (HSRs) and specific ICM and characterize the spectrum of ICM-related HSRs.
We performed a disproportionality analysis and proportionality test to assess the safety profile of ICM-related HSRs and compare the frequency ratio of specific HSRs in diverse age, sex, and country subgroups. We used reports downloaded from the US Food and Drug Administration Adverse Event Reporting System and data on the national use of individual ICM for this analysis.
A total of 11,343,365 adverse event reports were collected from the first quarter of 2013 to the first quarter of 2021, among which 5,432 cases were identified as ICM-induced HSRs. All of the studied ICMs were associated with overreporting frequencies of HSRs, in which iomeprol showed the highest reporting odds ratio (ROR) of 24.75 (95% CI, 19.61-31.24). Iopromide (ROR = 22.29; 95% CI, 20.18-24.62) and ioversol (ROR = 20.85; 95% CI, 18.54-23.44) were more likely to cause angioedema than other ICMs, particularly in the group aged 45 to 64 years. Iomeprol was associated with the largest disproportionality for severe cutaneous adverse reactions (ROR = 127.90; 95% CI, 103.32-159.88), whereas iodixanol exhibited maximal incidence when total use cases were considered. Regarding anaphylactic shock, iopamidol presented the highest disproportionality (ROR = 31.11; 95% CI, 27.15-35.65), especially in males or seniors aged greater than 65 years, whereas iopromide resulted in the maximum frequency in China and the United States.
Different ICMs exhibited diverse profiles regarding HSRs, which could be further affected by age, sex, or geographic area. Prospective studies are required for patient safety.

View all citing articles on Scopus

Disclosures: Authors have nothing to disclose.

Funding: This study was supported by Jerini AG (Berlin, Germany).

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Original Articles: Systemic Allergic DisordersMulticenter study of patients with angiotensin-converting enzyme inhibitor-induced angioedema who present to the emergency department

Background

Objective

Methods

Results

Conclusion

Section snippets

INTRODUCTION

MATERIALS AND METHODS

Frequency of ACEI-Induced Angioedema

DISCUSSION

Airway compromise due to angiotensin-converting enzyme inhibitor-induced angioedema: clinical experience at a large community teaching hospital

Chest

Drug-induced angioedema without urticaria

Drug Saf

Prescribing pattern of antihypertensive drugs in primary care units in turkey: results from the TURKSAHA study

Eur J Clin Pharmacol

Angiotensin II receptor blockers in patients with ACE inhibitor-induced angioedema

Ann Pharmacother

ACE inhibitor-induced angioedema. incidence, prevention and management

Drug Saf

Angioedema in heart failure: occurrence with ACE inhibitors and safety of angiotensin receptor blocker therapy

Congest Heart Fail

Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial

Am J Hypertens

Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy: a review of the literature and pathophysiology

Ann Intern Med

Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema

Clin Pharmacol Ther

Angioedema: the role of ACE inhibitors and factors associated with poor clinical outcome

Intensive Care Med