A novel approach to study the impact of ethnicity on reporting of cough/angioedema with RAS inhibitors in VigiBase

Background: Cough and angioedema are adverse events associated with especially angiotensinconverting enzyme (ACE) inhibitors but also reported with angiotensin receptor blockers (ARBs) and aliskiren, a direct renin inhibitor (DRI). Susceptibility of developing cough/angioedema with ACE inhibitors depends on ethnicity, which is not documented in spontaneous reporting systems of drug safety. Objectives: To assess the impact of ethnicity on the occurrence of cough/angioedema with renin angiotensin system (RAS) inhibitors using information reported to the the World Health Organization database (VigiBase). Methods: A case/non-case study was performed in VigiBase. Cases were defined as reports of cough/angioedema and non-cases were all reports of other adverse events. The reporting countries were divided into three categories: black African countries, East Asian countries and other countries. Logistic regression analysis was used to assess the association between reporting of cough/angioedema with each class of RAS inhibitors stratified by country group and to control for confounding. Results: The reporting of cough with ACE inhibitors was significantly higher in East Asian countries than black African countries and other countries (adjusted reporting odds ratios (RORs): 256, 95%CI (236-278), 48.9, 95%CI (42.7-56.1) and 35.4, 95%CI (34.8- 35.9), respectively. The reporting of angioedema with ACE inhibitors was significantly higher in black African countries than East Asian countries and other countries (adjusted RORs: 55.3, 95%CI (45.5-67.2), 5.29, 95%CI(3.89-7.21) and 16.5, 95%CI (16.1- 16.8), respectively. There was no difference in reporting of cough/angioedema with ARBs and DRI between black African countries, East Asian countries and other countries. Conclusions: Our results by grouping countries according to ethnicity in VigiBase are consistent with previous results in the literature suggesting that the occurrence of cough with ACE inhibitors is higher in East Asian patients and the occurrence of angioedema with ACE inhibitors is higher in black patients. These findings indicate that ethnicity should be included as scientific parameter in pharmacovigilance.