Association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder: US-based retrospective cohort study

Objective: To estimate the association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder (OAB).

Design: A retrospective claims-based study (2007-2015) of patients with OAB; outcomes from a subset were contrasted to a non-OAB comparison.

Setting: United States, commercially and Medicare-insured population.

Participants: 154 432 adults with OAB and 86 966 adults without OAB, mean age of 56 years, and 67.9% women.

Main outcome measures: Cumulative anticholinergic burden, a unitless value representing exposure over time, was estimated over the 12 months pre-index ('at baseline') and every 6 months post index. Burden was categorised as no burden (0), low burden (1-89), medium burden (90-499) or high burden (500+). Unadjusted rates of falls or fractures were estimated, and the increased risk associated with anticholinergic burden (measured at the closest 6-month interval prior to a fall or fracture) was assessed using a Cox proportional hazards model and a marginal structural model.

Results: Median (IQR) baseline anticholinergic burden was 30 (0.0-314.0) and higher among older (≥65 years, 183 [3.0-713.0]) versus younger (<65 years, 13 [0.0-200.0]) adults. The unadjusted rate of falls or fractures over the period was 5.0 per 100 patient-years, ranging from 3.1 (95% CI 3.0-3.2) for those with no burden, to 7.4 (95% CI 7.1-7.6) for those with high burden at baseline. The adjusted risk of falls and fractures was greater with higher anticholinergic burden in the previous 6 months, with an HR of 1.2 (95% CI 1.2 to 1.3) for low burden versus no burden, to 1.4 (95% CI 1.3 to 1.4) for high versus no burden. Estimates from marginal structural models adjusting for time-varying covariates were lower but remained significantly higher with a higher anticholinergic burden. Rates of falls and fractures were approximately 40% higher among those with OAB (vs those without).

Conclusion: Higher levels of anticholinergic burden are associated with higher rates of falls and fractures, highlighting the importance of considering anticholinergic burden when treating patients with OAB.