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. 2019 May 5;9(5):e026391.
doi: 10.1136/bmjopen-2018-026391.

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

Shelagh M Szabo  1 , Katherine Gooch  2 , Carol Schermer  2 , David Walker  2 , G Lozano-Ortega  1 , Basia Rogula  1 , Alison Deighton  1 , Edward Vonesh  3 , Noll Campbell  4
Affiliations

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

Shelagh M Szabo et al. BMJ Open. .

Abstract

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.

Keywords: anticholinergic burden; falls; fractures; marginal structural models; observational study; overactive bladder.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE form for Disclosure of Potential Conflicts of Interest (available on request from the corresponding author). SMS, GL-O, AD and BR declare a relevant conflict of interest for the work under consideration for publication as Broadstreet received funding from Astellas for the design and analysis of the data for this study; they declare no conflicts relative to financial activities outside of the submitted work, intellectual property or other relationships not covered. KC, CS and DW declare a relevant conflict of interest to the work under consideration for publication and for relevant financial activities outside of the submitted work as they are employees of Astellas Pharma, the funder of the study, at the time of study completion; they declare no conflicts relative to intellectual property or other relationships not covered. EV declares a relevant conflict of interest for the work under consideration for publication and for relevant financial activities outside of the submitted work as he received personal fees for consultancy for Astellas Pharma, the study funder; he declares no conflicts relative to intellectual property or other relationships not covered. NC declares a relevant conflict of interest for relevant financial activities outside of the submitted work as he received personal fees for consultancy for Astellas Pharma, the study funder; he declares no conflicts relative to the work under consideration for publication, intellectual property or other relationships not covered.

Figures

Figure 1
Figure 1
Mean (95% CI) level of anticholinergic burden according to time since cohort entry and age. ACB, anticholinergic burden.
Figure 2
Figure 2
Rates (top) and rate ratios (bottom), for falls and fractures* estimated over the study period in the overactive bladder cohort, according to baseline anticholinergic burden,** overall and according to age (<65 years vs >65 years); Truven MarketScan databases 2007–2015. *Point estimates (dots) and 95% CIs (lines) plotted. **Baseline anticholinergic burden assessed over the 12-month pre-index period. ACB, anticholinergic burden.
See this image and copyright information in PMC

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