Dubrall Diana, Branding Nora L, Mathey Carina M, Weber Anna M, Steffens Michael, Below Maike, Schmid Matthias, Wedi Bettina, Wieczorek Dorothea, Amann Philipp M, Löffler Harald, Koch Lukas, Schöffl Clemens, Dickel Heinrich, Ganjuur Nomun, Hornung Thorsten, Buhl Timo, Aygören-Pürsün Emel, Wurpts Gerda, Greve Jens, Nöthen Markus M, Forstner Andreas J, Sachs Bernhardt
Institute for Medical Biometry, Informatics and Epidemiology, University Hospital of Bonn, Bonn, Germany.
Research Division, Federal Institute of Drugs and Medical Devices (BfArM), Bonn, Germany.
Clin Transl Allergy. 2025 May;15(5):e70058. doi: 10.1002/clt2.70058.
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.
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.
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.
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.
血管性水肿(AE)作为血管紧张素转换酶抑制剂(ACEi)或血管紧张素受体阻滞剂(ARB)潜在的危及生命的药物不良反应(ADR)很少发生。本研究的目的是在欧洲药物不良反应数据库EudraVigilance和vARIANCE研究数据库中调查与ACEi/ARB诱导的血管性水肿相关的非遗传因素。
vARIANCE研究队列包括114例患有ACEi或ARB诱导的血管性水肿的患者。此外,在ADR数据库EudraVigilance中识别出171例血管性水肿报告和4650例关于ACEi/ARB其他ADR的报告,后者作为参考组。计算比值比,并使用血管性水肿报告与参考报告进行逻辑回归分析。
年龄增加、吸烟、过敏和既往血管性水肿病史被确定为ACEi/ARB诱导的血管性水肿的相关因素。在大多数患者中,肿胀影响面部、嘴唇和舌头。在vARIANCE研究中,约70% 的血管性水肿发生在治疗1年后。在vARIANCE研究中,二分之一的患者(接受ACEi治疗的患者中有84.2%)以及EudraVigilance报告中三分之一的患者(接受ARB治疗的患者中有59.6%)因血管性水肿住院。
在这项药物流行病学研究中,我们发现某些个体患者相关因素之间存在小到中度的关联。作为未来展望,将非遗传关联因素与相应的遗传数据相结合可能为构建更强的个体风险评分提供一种选择。