A Cohort Study on Incidence and Factors Associated With Adverse Drug Reactions of Enalapril in Lusaka, Zambia.

Angiotensin-converting enzyme inhibitors (ACEIs) are widely prescribed but are associated with adverse drug reactions (ADR), including angioedema, which is typically reported in 0.1%-0.7%. Data from sub-Saharan Africa are limited. This study aimed to estimate the incidence and risk factors of enalapril-associated ADRs in a Zambian cohort, with particular focus on angioedema. We conducted an ambispective cohort study of 400 adults initiating enalapril at two tertiary hospitals in Lusaka, Zambia. Enalapril was the only ACEI available to the participants, and the primary outcome was the occurrence of enalapril-associated ADRs requiring treatment discontinuation or modification. Kaplan-Meier methods were used to estimate event-free survival, and Cox proportional hazards regression was used to identify factors associated with ADR occurrence. Angioedema occurred in 19/400 participants (4.8%). Overall, 22% (88/400) of participants experienced at least one ADR impacting treatment. The most frequent ADRs were cough (10.3%) and dizziness (5.0%). In multivariable analysis, male sex was independently associated with a lower risk of ADR (adjusted hazard ratio [aHR] 0.59, 95% CI 0.37-0.93). No significant associations were identified for the high rate of angioedema. The incidence of enalapril-associated angioedema in this cohort was substantially higher than that reported in global as well as African American populations. These findings have clinical relevance for prescribing and monitoring ACEIs in sub-Saharan African populations. Further studies are needed to confirm this signal and explore underlying mechanisms.