Epidemiology of ACE Inhibitor Angioedema Utilizing a Large Electronic Health Record

Banerji, Aleena; Blumenthal, Kimberly G.; Lai, Kenneth H.; Zhou, Li

doi:10.1016/j.jaip.2017.02.018

Cited by 91 publications

(89 citation statements)

References 34 publications

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“…ARBs and aliskiren-associated angioedemas occurred more often within the first month of therapy, whereas 46.2% of ACEi-associated angioedemas occurred even after one year of therapy. The occurrence of ACEi-associated angioedemas after several years of ACEi therapy is known [16,68]. In contrast, this is not described in literature for ARBs and aliskiren-associated angioedemas.…”

Section: Reported Smoking Habits Comedications and Clinical Phenotypmentioning

confidence: 99%

Angioedemas associated with renin-angiotensin system blocking drugs: Comparative analysis of spontaneous adverse drug reaction reports

et al. 2020

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Introduction Angioedema is a subcutaneous swelling typically affecting the face, larynx or pharynx. It is a known adverse drug reaction (ADR) of ACE inhibitors (ACEi), angiotensin-II-receptor blockers (ARBs) and aliskiren (renin inhibitor). Several studies have reported pathophysiological mechanisms and risk factors of ACEi-associated angioedemas, whereas little is known for ARBs and aliskiren. The aim of the study was to analyze comparatively ACEi versus ARBs and aliskiren angioedema reports contained in the European ADR database EudraVigilance with regard to reported risk factors and clinical phenotypes. Methods All spontaneous angioedema reports received between 01/2010-06/2017 reporting either an ACEi, ARB, or aliskiren as "suspected/interacting" drug were identified using the Standardized MedDRA Query "angioedema (narrow)". In order to perform a comparative analysis, odds ratios (ORs) were calculated for angioedema reports of ACEi (n = 3.194) versus ARBs (n = 687) and aliskiren (n = 162). Results More patients with a history of allergy were included in angioedema reports of ARBs (6.8%) and aliskiren (13.6%) versus ACEi (4.3%). "Urticaria" as an ADR was reported more frequently in angioedema reports of ARBs (18.5%) and aliskiren (9.0%) versus ACEi (5.0%). ACEi-associated angioedemas were more often designated as "life-threatening" compared to ARBs (OR 2.2 [1.6-2.9]) and aliskiren-associated angioedemas (OR 14.2 (3.5-57.4). Concomitant therapy with mTOR inhibitors (OR 4.3 [1.0-17.9]) and fibrinolytics (OR 7.8 [1.1-57.2]) was reported more often in ACEi versus ARBs angioedema reports.

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Section: Reported Smoking Habits Comedications and Clinical Phenotypmentioning

confidence: 99%

Angioedemas associated with renin-angiotensin system blocking drugs: Comparative analysis of spontaneous adverse drug reaction reports

et al. 2020

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“…Angiotensin converting enzyme inhibitors (ACEi) are widely prescribed in the USA. ACEi -induced angioedema occurs in 0.1% to 0.7% of ACEi users [1,2]. ACE inhibitors are among the leading causes of druginduced angioedema in the United States in addition to Non-Steroidal Anti-Inflammatory Drugs.…”

Section: Discussionmentioning

confidence: 99%

Acute Respiratory Failure Secondary to ACE Inhibitor–Induced Angioedema after Five Years of Lisinopril Therapy

Sharman¹,

Song²,

Zawit³

et al. 2019

AJMCR

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Angiotensin-converting enzyme (ACE) inhibitors are amongst the commonest prescribed medications in the United States and considered to be the leading causes of drug induced angioedema. High bradykinin levels stimulate vasodilation and increased vascular permeability of the post-capillary venules and allow for plasma extravasation into the submucosal tissue, leading to angioedema. Usually, the angioedema occurs within the first week of exposure to therapy, but cases occurring after years of stable ACE inhibitor usage are not uncommon. Here, we present a 43-year-old Caucasian female who developed acute respiratory failure requiring mechanical ventilation secondary to ACEi-induced angioedema after five years of Lisinopril usage. This case will help to increase physicians' awareness that this potentially fatal complication can still occur after years of ACE inhibitor usage.

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“…Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) containing medications are often used for hypertension, heart failure and diabetes complications, and currently 14% of the population in Sweden is treated with these drugs [1]. Although being mostly effective and safe, around 0.2-0.7% of patients starting an ACEi, and 0.1-0.2% starting an ARB experience the adverse drug reaction (ADR) angioedema [2][3][4][5][6]. Compared with other populations, the risk is higher in African Americans, suggesting a genetic effect modification [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment

et al. 2020

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Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 × 10 −5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 × 10 −8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05-2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi-and ARBinduced angioedema.

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Epidemiology of ACE Inhibitor Angioedema Utilizing a Large Electronic Health Record

Abstract: Background-Angiotensin-converting enzyme inhibitors (ACEI) are a common cause of druginduced angioedema in the United States. Most epidemiologic ACEI angioedema data are from large multi-center clinical trials.

Cited by 91 publications

References 34 publications

Angioedemas associated with renin-angiotensin system blocking drugs: Comparative analysis of spontaneous adverse drug reaction reports

Angioedemas associated with renin-angiotensin system blocking drugs: Comparative analysis of spontaneous adverse drug reaction reports

Acute Respiratory Failure Secondary to ACE Inhibitor–Induced Angioedema after Five Years of Lisinopril Therapy

Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment

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