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. 2025 May;15(5):e70058.
doi: 10.1002/clt2.70058.

Non-genetic factors associated with ACE-inhibitor and angiotensin receptor blocker-induced angioedema

Diana Dubrall  1   2 , Nora L Branding  2   3 , Carina M Mathey  2   3 , Anna M Weber  2   3 , Michael Steffens  2 , Maike Below  4 , Matthias Schmid  1 , Bettina Wedi  5 , Dorothea Wieczorek  5 , Philipp M Amann  6   7 , Harald Löffler  6   7 , Lukas Koch  8 , Clemens Schöffl  8 , Heinrich Dickel  9 , Nomun Ganjuur  9 , Thorsten Hornung  10 , Timo Buhl  11 , Emel Aygören-Pürsün  12 , Gerda Wurpts  13 , Jens Greve  14 , Markus M Nöthen  3 , Andreas J Forstner  3   15 , Bernhardt Sachs  2   16
Affiliations

Non-genetic factors associated with ACE-inhibitor and angiotensin receptor blocker-induced angioedema

Diana Dubrall et al. Clin Transl Allergy. 2025 May.

Abstract

Background: Angioedema (AE) rarely occurs as a potentially life-threatening adverse drug reaction (ADR) to angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). The aim of the present study was to investigate non-genetic association factors with ACEi-/ARB-induced angioedema in the European ADR database EudraVigilance and the database of the vARIANCE study.

Methods: The cohort of the vARIANCE study comprised 114 patients who suffered from ACEi- or ARB-induced angioedema. In addition, 171 angioedema reports and 4650 reports on other ADRs of ACEi/ARB were identified in the ADR database EudraVigilance with the latter serving as a reference group. Odds ratios were calculated and a logistic regression analysis was performed using angioedema versus reference reports.

Results: Increased age, smoking, allergies and a history of previous angioedema were identified as associated factors for ACEi-/ARB-induced angioedema. In most patients, the swelling affected the face, lips and tongue. In the vARIANCE study, about 70% of angioedema occurred after 1 year of treatment. For one in two patients in the vARIANCE study (84.2% with ACEi treatment) and one in three patients from the EudraVigilance reports (59.6% with ARB treatment), the angioedema resulted in hospitalization.

Conclusions: We found small to moderate associations with certain individual patient-related factors in this pharmaco-epidemiological study. As a future perspective, combining non-genetic association factors with corresponding genetic data might provide an option to compose stronger and individual risk scores.

Keywords: angioedema; angiotensin‐converting enzyme inhibitors; angiotensin‐receptor blockers; drug‐induced angioedema; spontaneous reports.

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Conflict of interest statement

MMN has received fees for membership in the advisory board from HMG Systems Engineering GmbH (Fürth, Germany) and in the Medical‐Scientific Editorial Office of the Deutsches Ärzteblatt, for review activities from the European Research Council (ERC), and for serving as a consultant for EVERIS Belgique SPRL in a project of the European Commission (REFORM/SC2020/029). MMN receives salary payments from Life & Brain GmbH and holds shares in Life & Brain GmbH.

Figures

FIGURE 1
FIGURE 1
Identification of ADR reports in EudraVigilance and cases from the vARIANCE study.
See this image and copyright information in PMC

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