Antimuscarinics, also known as oral anticholinergics, form the first-line of pharmacotherapy for overactive bladder (OAB). Among older adults (65 years of age or older), the use of antimuscarinics must be carefully considered due to known impacts of cumulative anticholinergic exposure (“anticholinergic burden”), including increased risk of falls/fractures, and cognitive concerns. However, little is known regarding the extent of anticholinergic burden among nursing home residents with OAB. This study aimed to characterize the prevalence of and factors associated with cumulative anticholinergic burden among long-stay nursing home (LSNH) residents with OAB.

The study involved retrospective analysis of the Minimum Data Set (MDS) – linked Medicare claims data from 2013-2015, involving Parts A, B and D. LSNH residents (defined as having least 1 nursing home episode lasting at least 101 consecutive days), aged 65 years or older at index date (nursing home admission) were identified as having OAB based on the ICD-9/10 codes in inpatient or outpatient settings, or a claim for an OAB-specific medication (darifenacin, fesoterodine, oxybutynin, solifenacin, tolterodine, trospium chloride, mirabegron, onabotulinumatoxinA) based on prescription fill records/CPT codes during the study period. Additionally, all individuals were required to have medical/pharmaceutical coverage 6 months before and a minimum of 12 months following admission, and at least 180 days of nursing home stay after the 100th day of admission. The follow-up of 180 days post 100th day of admission was selected to capture anticholinergic burden because medication exposure in this study was ascertained using only Medicare Part D data, and medications for the first 100 days are usually covered by Medicare Part A.
Anticholinergic medication use was assessed over a 6-month period starting from the 100th day of admission, and anticholinergic burden was defined using the 4-point Anticholinergic Cognitive Burden (ACB) scale [range: 0 (none) – 3 (severe) anticholinergic activity]. Cumulative anticholinergic exposure was calculated as a product of the standardized daily dose (SDD) and the ACB scale score of individual medications to yield a drug- and patient-specific measure of standardized daily anticholinergic exposure (SDACE). The SDACE for multiple medications was then used to estimate a Summative Standardized Daily Anticholinergic Exposure (SumSDACE) measure across all 6-months of follow-up per patient. The anticholinergic burden was categorized as no (0), low (1-89), moderate (90-499) or high (500 and greater), based on the distribution of SumSDACE scores. The Andersen Behavioral Model (ABM) was used to identify the predisposing (age, sex, race/ethnicity, marital status), enabling (dual eligibility, geographical region, urban-rural residence) and need factors (baseline co-medications such as anticholinergics, antidepressants, antipsychotics, anti-hypertensives; comorbidities such as fall/fracture, neurogenic bladder, multiple sclerosis, Elixhauser comorbidities, BMI, urinary incontinence, bowel incontinence, cognitive performance, depressed mood indicator) associated with high cumulative anticholinergic burden. These factors were selected based on past literature and availability in Medicare and MDS databases.

Descriptive statistics were used to summarize the prevalence and distribution of the anticholinergic burden among LSNH residents with OAB. The analysis included bivariate comparisons across levels of cumulative anticholinergic burden based on SumSDACE scores. Differences between the varying levels of cumulative anticholinergic burden were evaluated via Analysis of Variance (ANOVA) and chi-squared tests, for continuous and categorical variables, respectively. Two multivariable logistic regression models were developed. The logistic regression model aimed to identify the predictors of anticholinergic burden by grouping the outcome into two levels - moderate/high (90 and greater) vs low/no (0-89) anticholinergic burden. The multinomial logistic regression model evaluated the predictors of moderate (90-499) and high (500 and greater) burden compared to low burden (1-89). Both models were adjusted for factors included in the ABM framework.

A total of 124,345 individuals were identified as LSNH residents with OAB; 45.4% of patients were 85 years of age or older, 72.7% were female, and 87.3% were non-Hispanic White. Of them, 123,308 patients (99.1%) had at least one medication claim during follow-up and formed the analytical sample. Most (87.2%) of these patients had some anticholinergic burden; 12.8% had none, 18.0% had low, 41.9% had moderate, and 27.3% had high cumulative anticholinergic burden. The distribution of burden levels varied by several predisposing, enabling, and need factors. 
Results from the logistic regression revealed several factors associated with moderate/high vs low/no burden (Table 1). Among the predisposing factors, age was negatively associated with moderate/high burden (age 75–84 years: odds ratio [OR] 0.75; 95% CI 0.72 - 0.78]; 85 years and older: OR 0.64; 95% CI 0.61 - 0.67), whereas females were positively associated with having moderate/high burden compared to males (OR 1.25; 95% CI 1.21 - 1.29). Compared to non-Hispanic Whites, Blacks, Hispanics and other racial groups were less likely to have moderate/high burden. Of the enabling factors, dual eligibility increased the likelihood of having moderate/high burden (OR 1.16; 95% CI 1.13 - 1.20). The odds of having moderate/high burden significantly decreased among LSNH residents located in the Northeast (OR 0.89; 95% CI 0.86 - 0.93) and West regions (OR 0.82; 95% CI 0.78 - 0.86) compared to South, and residence in urban vs rural areas (OR 0.83, 95% CI 0.81 - 0.86). Among the need factors, history of multiple sclerosis, neurogenic bladder, Elixhauser comorbidities (such as heart failure, cardiac arrhythmias, hypertension, diabetes, depression, psychoses, obesity), baseline co-medication use including anticholinergics, higher BMI levels, occasional/frequent urinary incontinence and depressed mood indicators increased the odds while cognitive impairment, bowel incontinence reduced the odds of having moderate/high burden. 

These findings were maintained and often strengthened in the multinomial logistic regression model (Table 2). Females were positively associated with having moderate vs low burden (OR 1.16; 95% CI 1.11 - 1.21) and high vs low burden (OR 1.40; 95% CI 1.33 - 1.46), whereas older age groups  and non-White race were negatively associated with higher burden levels. With respect to enabling factors, dual eligibility significantly increased the likelihood of moderate and high burden levels, whereas Northeast and West (vs South) regions as well as residence in urban (vs rural) areas decreased the likelihood of having moderate and high burden levels. Of the need factors, prior history of multiple sclerosis, neurogenic bladder, Elixhauser comorbidities, baseline co-medication use, higher BMI levels, and occasional/frequent urinary incontinence were positively associated with the likelihood of moderate and high burden, while cognitive impairment decreased the likelihood of higher burden. Overall, a dose-response relationship was observed with respect to the magnitude of association for high vs low burden compared to moderate vs low burden for all predisposing and enabling factors, and the above need factors.

Results from this national-level study using nursing home –linked Medicare data suggests that nearly 90% of LSNH residents with OAB were exposed to varying levels of anticholinergic burden. Although increasing age is often considered associated with increasing anticholinergic burden, in the present study, younger age in addition to prior history of co-medications and several comorbidities were significantly associated with moderate and or high anticholinergic burden.

Anticholinergic burden is prevalent among LSNH residents with OAB and raises concerns regarding prescribing practices in these patients because of the potential adverse effects of anticholinergics. Concerted efforts are needed to reduce anticholinergic burden in this population, particularly among those with underlying comorbidities.