Higher anticholinergic burden is associated with increased medium‐ and long‐term mortality following hip fracture: A systematic review and meta‐analysis
Alejandro Valcuende‐Rosique, Elisa García Tercero, Ana Navalon Bono, Joaquín Borrás‐Blasco, Angel Belenguer Varea, Juan María De la Cámara‐de Las Heras, Magdalena Linge Martin, Francisco José Tarazona‐SantabalbinaAim
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.