Higher anticholinergic burden is associated with increased medium- and long-term mortality following hip fracture: A systematic review and meta-analysis.

AIM: Anticholinergic medications are frequently prescribed to older adults and are associated with adverse outcomes including cognitive impairment, delirium and mortality. In patients with hip fracture-a population characterized by frailty and polypharmacy-the impact of anticholinergic burden on survival remains uncertain. This study aimed to examine the association between anticholinergic burden and all-cause mortality after hip fracture in adults aged ≥65 years.

METHODS

A systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines (PROSPERO CRD420251181616). PubMed, Embase, Scopus and Cochrane Library were searched through September 2025. Observational studies assessing mortality by validated anticholinergic burden scales-Anticholinergic Cognitive Burden (ACB), Anticholinergic Risk Scale (ARS) or Drug Burden Index (DBI)-were included. Pooled hazard ratios (HR) with 95% confidence intervals were calculated using a random-effects model.

RESULTS

Five cohort studies including 65 435 patients met inclusion criteria. High anticholinergic burden was associated with increased 12-month (HR = 1.47; 95% CI 1.11-1.94; p = 0.006) and 36-month mortality (HR = 1.45; 95% CI 1.05-2.00; p = 0.02). No significant association was observed at 1-6 months. Overall, pooled analysis showed a 40% higher mortality risk in patients with high anticholinergic burden (HR = 1.40; 95% CI 1.22-1.61; p < 0.001). Heterogeneity was high, and the certainty of evidence ranged from low to very low.

CONCLUSION

Higher anticholinergic burden was associated with an increased risk of medium- and long-term mortality after hip fracture in older adults. Routine assessment and reduction of anticholinergic exposure should be incorporated into perioperative geriatric management to improve survival outcomes.