The impact of age and sex on the reporting of cough and angioedema with renin–angiotensin system inhibitors: a case/noncase study in VigiBase

Abstract

The purpose of this study was to assess the impact of age and sex on the reporting of cough and angioedema related to renin-angiotensin system (RAS) inhibitors. A case/noncase study was performed in VigiBase. Two case groups were identified, reports of cough and reports of angioedema, and noncases were all reports of all other adverse events. Logistic regression analysis was used to assess the association between reporting of cough and angioedema with each class of RAS inhibitors stratified by age/sex and to control for confounding. The reporting of cough with angiotensin-converting enzyme (ACE) inhibitors was significantly higher in women than in men [adjusted reporting odds ratio (ROR): 44.0, 95% CI (43.2-44.8) for women vs. 29.2, 95% CI (28.5-29.9) for men]. There was no difference in reporting of cough linked to angiotensin receptor blockers (ARBs) and aliskiren between men and women. In contrast, the reporting of angioedema with ACE inhibitors and ARBs was significantly higher in men than in women, but for aliskiren, women had a significantly higher ROR than men [adjusted ROR: 5.20,) for women vs. 3.04, 95% CI (2.30-4.02) for men]. The reporting of cough with ACE inhibitors was increased with age until reaching a plateau at middle adulthood (40-59 years) and the reporting of angioedema with ACE inhibitors was increased with age until elderly (60-79 years). Age had only a slight effect on the reporting of cough and angioedema with ARBs and aliskiren. Both age and sex have substantial effects on the reporting of cough and angioedema with RAS inhibitors and in particular ACE inhibitors. Further study is needed to determine whether these differences mainly express different adverse drug reaction risks in subgroups or also can be explained by factors influencing reporting.

The presence of underlying asthma should be investigated in patients diagnosed with ACE inhibitor induced cough

“…In our study, female sex was also significantly higher and smoking rates were significantly lower in the study group compared to controls. These results corroborate the results of previous studies on this subject and interestingly also studies dealing with the profiles of asthma . Also, GERD symptoms were significantly higher in patients with ACE‐I induced cough.…”

“…ACE‐I‐induced cough is predominantly seen in females and nonsmokers . In our study, female sex was also significantly higher and smoking rates were significantly lower in the study group compared to controls.…”

“…ACE-I-induced cough is predominantly seen in females and nonsmokers. 2,[27][28][29][30][31] In our study, female sex was also significantly higher and smoking rates were significantly lower in the study group compared to controls. These results corroborate the results of previous studies on this subject and interestingly also studies dealing with the profiles of asthma.…”

“…These results corroborate the results of previous studies on this subject and interestingly also studies dealing with the profiles of asthma. 2,18,[27][28][29][30][31] Also, GERD symptoms were significantly higher in patients with ACE-I induced cough. Symptoms and/or diagnosis of GERD are more common in people with asthma compared to the general population.…”

Cyclo‐oxygenase selectivity and chemical groups of nonsteroidal anti‐inflammatory drugs and the frequency of reporting hypersensitivity reactions: a case/noncase study in VigiBase

“…For US reports, we found differences in RORs of HSRs for sulfonamide NSAIDs compared with our primary analyses. Differences in reporting habits and ethnicity might explain these differences as well as NSAID sales and consumptions between countries. For example, only celecoxib among coxibs is still available in the US market .…”