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.
- anticholinergic burden
- overactive bladder
- observational study
- marginal structural models
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Contributors SMS and KG were responsible for the conception and design of the work. SMS, GL-O, BR and AD were responsible for data collection. SMS, GL-O, BR, KG, CS, DW, EV, NC and AD were responsible for data analysis and interpretation. SMS was responsible for drafting the article. SMS, KG, CS, DW, GL-O, BR, AD, EV and NC were responsible for critical revision of the article; were responsible for final approval of the version to be published.
Funding The present study was initiated by Astellas Pharma Global Development, and funding for the conduct of this study was provided by Astellas Pharma Global Development. Publication of the study results was not contingent on permission from the sponsor.
Disclaimer KG, CS and DW were employees of Astellas Pharma Global Development at the time of study completion. SMS, GL-O, BR and AD were employees of Broadstreet Health Economics & Outcomes Research, which received payment from Astellas to conduct the study. EV and NC received payment from Astellas for consultation.
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.
Ethics approval Because the Truven MarketScan data are deidentified and are fully Health Insurance Portability and Accountability Act of 1996 compliant, and because this study did not involve the collection, use or transmittal of individually identifiable data, Institutional Review Board review or approval was not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The authors confirm that all data required to replicate our findings are available for purchase by any researcher from Truven Marketscan via this link: https://marketscan.truvenhealth.com/marketscanportal/
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