Association between drugs with anticholinergic effects and mortality in patients on hemodialysis

Abstract

Patients undergoing hemodialysis frequently receive medications with anticholinergic effects, yet evidence linking cumulative anticholinergic burden to outcomes in this population is scarce. While general population studies associate anticholinergic burden with adverse outcomes, it remains unknown whether the same holds true in patients undergoing hemodialysis. We examined whether anticholinergic burden is associated with mortality and morbidity in patients undergoing hemodialysis. We analyzed data from 6069 adults (mean age 65 years, 34% women) in the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS) cohort (2009–2018). Baseline anticholinergic burden was assessed using the Anticholinergic Cognitive Burden (ACB) score; patients were categorized as ACB ≥ 1 versus 0. The primary outcome was all-cause mortality; secondary outcomes included fracture-related hospitalization, cardiovascular events, self-reported falls, and quality of life (QOL) changes measured by the Short-Form 12-Item Health Survey (SF-12). Analyses used Cox and multivariable regression, adjusting for demographics, comorbidities, and polypharmacy. At baseline, 50.4% of patients had ACB scores ≥ 1. During 2.1-year mean follow-up, 707 deaths occurred. The adjusted hazard ratio for mortality (ACB ≥ 1 versus 0) was 0.92 (95% confidence interval [CI] 0.78–1.08; P = 0.31). No dose–response relationship was observed. Anticholinergic burden was not significantly associated with fracture-related hospitalization (adjusted odds ratio [OR] 1.31, 95% CI 0.94–1.83), cardiovascular events (OR 1.13, CI 0.96–1.33), falls (OR 0.92, CI 0.73–1.15), or QOL changes. In this hemodialysis cohort, anticholinergic burden was not associated with increased mortality or adverse outcomes, contrasting with general population findings. These results do not establish safety of individual anticholinergic agents; rather, they suggest that overall burden did not drive adverse outcomes in this population. Judicious prescribing remains warranted until further evidence from studies incorporating dialysis-specific factors becomes available.