Persistence with cholinesterase inhibitor therapy in a population-based cohort of patients with Alzheimer's disease

Abstract

Purpose: To estimate the risk (and determinants) of discontinuing cholinesterase inhibitors (ChEIs) in a population-based sample of Alzheimer's disease (AD) patients.

Methods: This is a retrospective cohort study based on linked de-identified administrative health data from the province of Saskatchewan, Canada. The cohort included all AD patients receiving a ChEI prescription during the first year of provincial coverage (2000-2001). Persistence was defined as no gap of 60+ days between depletion and subsequent refill of a ChEI prescription. Kaplan-Meier analysis was used to estimate the risk of discontinuation over 40 months. Cox regression with time-varying covariates was used to assess risk factors for ChEI discontinuation.

Results: The sample included 1080 patients (64% female, average age 80 +/- 7 years). Baseline mean (SD) Mini-Mental State Examination (MMSE) and Functional Activities Questionnaire (FAQ) scores were 20.8 (4.4) and 17.5 (7.7), respectively. Over 40 months, 84% discontinued therapy. The 1-year risk of discontinuation was 66.4% (95%CI 63.5-69.3%). Discontinuation was significantly more likely for females (adjusted HR 1.34, 95%CI 1.16-1.55) and among those with lower MMSE scores (2.52, 2.01-3.17 if <15), not receiving social assistance (1.25, 1.07-1.45), and paying at least 65% of total prescription costs (1.51, 1.30-1.74). It was significantly less likely for patients with frequent physician visits (0.78, 0.66-0.93, for 7-19 vs. <7 visits), higher Chronic Disease Scores (0.74, 0.61-0.89, for 7+ vs. <4), and FAQ scores of 9+ (0.82, 0.69-0.99).

Conclusion: The likelihood of discontinuing ChEI therapy was high in this real-world sample of AD patients. Significant predictors included clinical, socioeconomic, and practice factors.