Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE credits
Angiotensin converting enzyme inhibitor -induced angioedema- identification of possible risk factors
Author: Julia Nagy Supervisor: Pär Hallberg, Department of Clinical Pharmacology, Uppsala University Hospital, Uppsala Examiner: Nielsen. E Master of Clinical Pharmacy 2015 Department of Pharmaceutical Bioscience, Division of Pharmacokinetics and Drug Therapy, Faculty of Pharmacy, Uppsala University, Sweden
Background and Objective Angioedema is a sudden swelling of the skin and mucosal membranes; a swelling affecting the upper airways; can be life-threatening and is a known adverse drug reaction (ADR) of angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs). The pathogenesis is poorly understood and little is known about the possible risk factors. Design Exploratory case-control study. Patients with ACEi-induced angioedema were compared with a) patients who had experienced ACEi-induced cough, b) patients with ARB-induced angioedema, and c) controls tolerant to ACEi-treatment.
Setting Raw data was extracted from the SWEDEGENE database including patients with ACEi- or ARB-induced angioedema and ACEi-induced cough identified between 2010-2015 in Sweden, mostly through the Swedish national database of spontaneously reported ADRs.
Main outcome measures The aim of this research was to identify possible risk factors for ACEi-induced angioedema and to increase the understanding of the pathogenesis behind this ADR.
Results Selective calcium channel blockers with mainly vascular effects were statistically significantly more common among cases of ACEi-angioedema than cough (33.8% vs 12.4%, OR 3.6 [95% CI 1.9-6.8], p = 3.57 ×10-5). Smoking (30.7% vs 8.3%, OR 4.9 [95% CI 2.4-10.2], p= 4.51 ×10-6) was also more common. Malignant cancer was statistically significantly more common among cases of ACEi angioedema than ARB angioedema (15.8% vs 0%, p = 0.0233), as was smoking (29.3% vs 6.7%, OR 5.8 [95% CI 1.3-25.4], p=0.0106). There was also a borderline statistically significant difference between ACEi-angioedema and ACEi-tolerant controls regarding malignant cancer (16.2% vs 3.0%, OR 6.2 [95% CI 0.8-47.1], p=0.0531). Classification of cancers into ongoing or previous showed a greater proportion of ongoing cancer disease among patients with ACEi-induced angioedema than cough (6.5% vs 0%, p=0.0157). A similar difference was seen for ACEi-induced vs ARB-induced angioedema (5.7% vs 0%) and ACE-induced angioedema vs tolerant controls (5.6% vs 3.0%), although not statistically significant.
Conclusions Smoking, malignant cancer and concomitant treatment with selective calcium channel blockers were identified as possible risk factors for ACEi-induced angioedema. These findings could help to increase the understanding of the pathogenesis behind ACEi-induced angioedema, but would need confirmation in other studies.