Antimuscarinic Cascade Across Individual Cholinesterase Inhibitors in Older Adults with Dementia

Background Acetylcholinesterase inhibitors (AChEIs) have been associated with an increased risk of starting antimuscarinic treatment to treat overactive bladder (OAB)-an example of a prescribing cascade. Limited comparative data exist regarding the prescribing cascade of antimuscarinics across individual AChEIs in older adults with dementia. Objective This study examined the association between individual AChEI use and antimuscarinic cascade in older adults with dementia. Methods We conducted a new user retrospective cohort study from January 2005 to December 2018 using data from the TriNetX electronic medical record database, a federated electronic medical records network in the US. The cohort included patients 65 years or older with a diagnosis of dementia using AChEIs (donepezil, galantamine, or rivastigmine). Individual AChEIs were identified with index dates from 1 January 2006 to 31 June 2018, with a 1-year washout period. The study excluded patients with any antimuscarinic use and OAB diagnosis 1 year before the AChEI index date. The primary outcome of interest was the prescription of antimuscarinics within 6 months of the AChEI index date. A Cox proportional hazard model was used to assess the association between individual incident AChEI use and antimuscarinic prescribing cascade after controlling for several covariates. Results The study included 47,059 older adults with dementia who were incident users of AChEIs. Most of these patients were initiated with donepezil (83.1%), followed by rivastigmine (12.3%) and galantamine (4.6%). Overall, 8.16% of the study cohort had incident OAB diagnosis or antimuscarinic prescription. Antimuscarinics were initiated by 1725 (3.7%) older adults with dementia within 6 months of AChEI prescription, and cascade varied widely across individual agents-donepezil (3.9%), rivastigmine (2.6%), and galantamine (2.9%). Cox proportional hazard analyses revealed that donepezil users had an increased risk of receiving antimuscarinics (adjusted hazard ratio 1.55, 95% confidence interval 1.31-1.83) compared with rivastigmine. The findings were consistent in sensitivity analyses. Conclusion This study found that donepezil use is more likely to lead to antimuscarinic cascade than rivastigmine. Future studies are needed to determine the potential consequences of this cascade in dementia.

Automated summary

This study found that donepezil use is more likely to lead to antimuscarinic cascade than rivastigmine in older adults with dementia. Further research is needed to investigate the potential consequences of this cascade in dementia.