Abstract:

OBJECTIVES: To examine dose-related prescribing and short-term serious events associated with initiation of cholinesterase inhibitor (ChEI) therapy. DESIGN: Retrospective, population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women (n=47,829) and men (n=32,503) aged 66 and older who initiated a ChEI between April 1, 2010, and June 30, 2016. MEASUREMENTS: All-cause serious events (emergency department (ED) visits, inpatient hospitalizations, death) within 30 days of ChEI initiation. Multivariable Cox proportional hazards models were used to estimate adjusted rates of serious events. RESULTS: Overall, 4.8% of older adults were dispensed a lower-than-recommended ChEI starting dose, 87.9% a recommended dose, and 7.3% a higher-than-recommended starting dose. Eight thousand six hundred seventy-one (10.8%) individuals experienced a serious event within 30 days of initiating therapy, primarily ED visits (8,540, 10.6%). Relative to those initiated on a recommended starting dose, those initiated on a higher dose had a significantly increased rate of serious events (women adjusted hazard ratio (aHR) 1.50, 95% confidence interval (CI) =1.38-1.63; men aHR 1.31, 95% CI=1.19-1.45). Similar patterns were found for ED visits and inpatient hospitalizations but not death. The relative effect of higher-than-recommended starting dose dispensed vs. recommended starting dose dispensed was greater in women than it was in men: the number needed to harm was 22 (95% confidence interval (CI)=18-29) for women and 36 (95% CI= 26-61) for men. CONCLUSION: Serious events immediately after initiation of ChEIs were associated with starting ChEI dose. This association was stronger in women.