(A-127) Comparative 1‐Year Survival Among Hypertensive Alzheimer’s Disease Patients Receiving Donepezil Versus Memantine: A Target Trial Emulation Study

Background: The impact of anti‐dementia medications on short‐term survival in patients with Alzheimer’s disease (AD) and comorbid hypertension remains uncertain. In addition to their cognitive effects, emerging evidence suggests that donepezil might reduce hypertension while memantine may increase it, potentially influencing survival outcomes in this vulnerable population.

Objectives: To compare the 1‐year survival outcomes between hypertensive AD patients initiating donepezil monotherapy versus those receiving memantine monotherapy.

Methods: We emulated a pragmatic, open‐label target trial using the Medical Information Mart for Intensive Care (MIMIC)-IV. Eligible patients were those with a diagnosis of hypertension and AD who initiated either donepezil or memantine as a single therapy; individuals with non‐AD dementias, recent use of investigational drugs, or combination therapy were excluded. The index date was defined as the patient’s first administration of the respective study medication, and treatment duration was computed over a 12‐month period. The primary outcome was 1‐year mortality. To adjust for potential confounding, we applied inverse probability weighting. Baseline covariates were incorporated into propensity score models. A marginal structural Cox proportional hazards model was then fitted to estimate hazard ratios (HRs) for comparing the treatments, along with their 95% confidence intervals (CIs), in an intention-to-treat analysis.

Results: A total of 327 eligible patients were included, of whom 222 (68%) received donepezil and 106 (32%) received memantine. The adjusted Cox model revealed a hazard ratio (HR) for treatment (memantine vs. donepezil) of (HR=1.12, 95% CI = 0.74–1.70). Additionally, heart failure was associated with an increased risk of mortality (HR = 1.98, 95% CI= 1.00–3.90) in this cohort.

Conclusions: The results indicate that donepezil and memantine monotherapy yield comparable 1‐year survival outcomes among hypertensive patients with Alzheimer’s disease. However, heart failure emerged as a significant predictor of increased mortality in this cohort.