An In-depth Analysis of the Retrospective Cohort Study Published in BMJ Open

In a groundbreaking study published in BMJ Open (DOI: 10.1136/bmjopen-2018-026391), researchers have unearthed a concerning association between anticholinergic drugs used to treat overactive bladder (OAB) and an increased risk of falls and fractures. This revelation brings to the fore a heretofore unappreciated drug safety issue, particularly for older adults.

This retrospective cohort study delved into the medical claims of a large population segment in the United States between 2007 and 2015. It included 154,432 adults diagnosed with OAB and a control group of 86,966 adults without the condition. The study conducted by Szabo et al., supported by Broadstreet Health Economics & Outcomes Research and Astellas Pharma Global Development Inc., highlights how an increased cumulative anticholinergic burden over time is seemingly linked to a rise in falls and fractures.

The Peril of Cumulative Anticholinergic Burden

The term ‘anticholinergic burden’ refers to the cumulative effect of taking one or more drugs that block acetylcholine, a neurotransmitter involved in various functions including muscle movement and memory. Anticholinergic medications are often prescribed for OAB to reduce muscle spasms of the bladder but are also evident in treatments for other conditions such as allergies, depression, and Parkinson’s disease.

In this large-scale observational study, anticholinergic burden was quantified based on prescription data. Researchers then categorized this burden into four distinct groups: no burden (0), low burden (1-89), medium burden (90-499), and high burden (500+). What they found was startling – as the anticholinergic burden increased, so did the rates of falls or fractures, unadjusted figures showing a range from 3.1 per 100 patient-years for those with no burden to 7.4 for those with high burden at baseline.

When adjustments were made for various risk factors, the study yielded a hazard ratio (HR) of 1.2 for a low anticholinergic burden and a HR of 1.4 for a high burden, indicating a significant rise in fall and fracture risk.

The OAB Challenge

OAB is a prevalent and distressing condition, especially among the elderly. Increased urgency and frequency of urination often necessitate medical intervention. Anticholinergic drugs, like oxybutynin and tolterodine, have been the cornerstone of pharmacological treatment. However, the newfound association with physical harm poses a fresh dimension to the OAB treatment decision matrix – the need to weigh the benefits of symptom control against the potential risk of physical injury due to falls or fractures.

The study results are particularly concerning for the older adult population. Prior research pointed out an association between anticholinergic medications and cognitive decline, further amplifying the potential risk when paired with an increased likelihood of falls – a leading cause of morbidity and mortality in the elderly.

Implications for Clinical Practice

This compelling evidence urges healthcare providers to be vigilant when prescribing anticholinergic medications for OAB, particularly in the geriatric population. It advocates for a personalized approach taking into account the patient’s fall risk and possibly opting for alternatives with a lower anticholinergic load.

Alternative Treatments

Recognizing the risk, it’s critical to explore alternative treatments for OAB that exhibit a lessened or nonexistent anticholinergic burden. Mirabegron, a beta-3 agonist, and pelvic floor muscle training are among the substitutes that could potentially mitigate the risk of falls and fractures without compromising the management of OAB.

A Call for Further Research

This study is a call to action for further research into the comprehensive health effects of anticholinergic medications. It underscores the need for prospective trials that could more definitively ascertain the causal relationship between anticholinergic burden and adverse physical outcomes.

Conclusion

The enlightening revelations from the study published in BMJ Open have significant implications for the management of overactive bladder, particularly in older adults. While anticholinergic medications are effective for OAB symptoms, they come with a heightened risk of falls and fractures. This information is pivotal for clinicians as they ponder the delicate balance of managing OAB’s disruptive symptoms while safeguarding their patients from potential harm.

References

1. Szabo, S.M., Gooch, K.L., Schermer, C.R., Walker, D.R., Lozano-Ortega, G., Rogula, B., … & Campbell, N.L. (2020). Association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder: US-based retrospective cohort study. BMJ Open, 10(5): e026391. DOI: 10.1136/bmjopen-2018-026391

2. Gray, S.L., Anderson, M.L., Dublin, S., … & Walker, R. (2015). Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med, 175(3), 401-407. DOI: 10.1001/jamainternmed.2014.7663

3. Hausdorff, J.M. (2005). Gait variability: methods, modeling and meaning. J Neuroeng Rehabil, 2, 19. DOI: 10.1186/1743-0003-2-19

4. Kao, L.T., Huang, C.Y., Lin, H.C., … & Hsu, C.Y. (2018). No increased risk of fracture in patients receiving antimuscarinics for overactive bladder syndrome: A retrospective cohort study. J Clin Pharmacol, 58(6), 727-732. DOI: 10.1002/jcph.1067

5. Richardson, K., Bennett, K., Maidment, I.D., … & Fox, C. (2015). Use of medications with anticholinergic activity and self-reported injurious falls in older community-dwelling adults. J Am Geriatr Soc, 63(8), 1561-1569. DOI: 10.1111/jgs.13543

Keywords

1. Overactive bladder treatment risks
2. Anticholinergic burden and falls
3. Elderly fall prevention
4. Non-anticholinergic OAB therapy
5. Medication-related fracture risk