NON-GENETIC factors such as age, allergies, smoking, and prior history of angioedema may significantly increase the risk of angioedema in patients taking ACE inhibitors or angiotensin receptor blockers, according to new pharmaco-epidemiological research. These drugs, commonly used to treat hypertension and heart failure, are known to rarely trigger angioedema—a potentially life-threatening adverse reaction characterized by rapid swelling of the face, lips, or tongue.
Drawing on data from the vARIANCE study and the EudraVigilance adverse drug reaction database, researchers evaluated a combined total of 114 patients with confirmed ACEi- or ARB-induced angioedema and over 4,800 reports of other adverse reactions to these medications. Logistic regression analysis revealed small to moderate associations between angioedema and specific non-genetic risk factors.
Among the findings, nearly 70% of angioedema cases in the vARIANCE cohort occurred after more than a year of treatment, highlighting the potential for delayed onset. Additionally, 50% of affected patients in the vARIANCE study and one-third of cases in EudraVigilance required hospitalization. ACE inhibitors were the primary trigger in the majority of cases leading to admission.
The authors emphasize the importance of recognizing patient-specific factors that could predispose individuals to severe adverse reactions. While genetic predispositions are being explored, these new findings suggest that a combined approach integrating both genetic and non-genetic data may ultimately help predict and prevent serious drug-induced angioedema.
Reference:
Dubrall D et al. Non-genetic factors associated with ACE-inhibitor and angiotensin receptor blocker-induced angioedema. Clin Transl Allergy. 2025;15(5):e70058.
