Geographic variation in dementia-related adverse events associated with sacubitril/valsartan: Analysis of the FDA Adverse Event Reporting System

Abstract This study aimed to investigate geographical variation in the risk of dementia-related adverse events (AEs) associated with sacubitril/valsartan. Cases from the FDA Adverse Event Reporting System involving patients aged 60 or older with sacubitril/valsartan or angiotensin receptor blockers (ARBs) were analyzed. The reporting odds ratios (RORs) for dementia-related AEs were calculated for each continent and the correlation between MME variants and ROR was analyzed. The risk of broad dementia associated with sacubitril/valsartan usage was significantly lower in Asia and Africa (ROR = 0.53, 95% CI = 0.31–0.91; ROR = 0.34, 95% CI = 0.12–0.96, respectively). The risk was significantly higher in North America (ROR = 1.3, 95% CI = 1.16–1.60). In Europe, the risk of broad dementia was significantly lower (ROR = 0.74, 95% CI = 0.59–0.93), while that of narrow dementia was significantly higher (ROR = 8.76, 95% CI = 2.27–33.90). A strong negative correlation was found between broad dementia risk and the frequency of the rs701109 polymorphism (r = -0.9) and the rs3736187 polymorphism (r = -0.88). There are regional variations in dementia-related AEs associated with sacubitril/valsartan usage, and differences in genetic polymorphisms could be a potential cause.