Memantine, acetylcholinesterase inhibitors, and quality‐of‐care outcomes among patients with cognitive impairment: an emulated trial design
Erin L. Ferguson, Jingxuan Wang, Justin S. White, Katherine Possin, Anna Chodos, Fan Xia, Eva Raphael, Alexander K. Smith, M. Maria GlymourAbstract
INTRODUCTION
We evaluated the effect of acetylcholinesterase inhibitors (AChEIs) and memantine on non‐cognitive outcomes by implementing emulated trials in electronic health records.
METHODS
Individuals diagnosed with cognitive impairment who initiated AChEIs or memantine were matched to up to five non‐initiators. Associations of medication initiation with 11 non‐cognitive outcomes were estimated using Cox proportional hazards models. We calculated e‐values for each hazard ratio (HR) and compared their magnitude to socioeconomic predictors of memantine and AChEI use in a US‐based cohort.
RESULTS
AChEI initiation was associated with nine of 11 adverse outcomes. For example, the HR for antipsychotic use = 1.67 (95% confidence interval [CI]: 1.51 to 1.84) and depression HR = 1.86 (1.67 to 2.06). Results for memantine were similar. E‐values varied from 1.45 to 2.11 for memantine and 1.40 to 2.44 for AChEIs. Many potential confounders had odds ratios (ORs) > 1.4 for initiation, including marital status (ORs = 1.36 to 6.67).
DISCUSSION
Memantine and AChEIs were associated with adverse outcomes, and residual confounding was unlikely to fully account for all the observed associations.