It is important to accurately establish the contribution that antimuscarinic agents can have on the anticholinergic burden experienced by older patients with OAB. By quantifying this, it may be possible to indicate whether the burden experienced by patients will have a substantial effect on their cognition and thus their quality-of-life. In this database study, we assessed anticholinergic burden and the contribution of antimuscarinic agents to the overall burden in patients aged ≥65 years in South Korea.
In our study, the 100-day cumulative ACB score was 15 times higher in the OAB group than the non-OAB group. A total of 64.3% of the ACB score in the OAB group was attributable to OAB medications. As expected, patients taking mirabegron only had an ACB score attributable to OAB medications of 0. In contrast, the highest percentage ACB score attributable to OAB medication was observed in the group of patients who took antimuscarinics only (66.9%). These findings align with the results of a previous Japanese pharmacy claims database analysis, which found that both the prevalence of anticholinergic burden scale-listed anticholinergic use and mean ACB scores were higher in patients with OAB versus patients without OAB [21]. Similarly, the patients who received antimuscarinics had higher ACB scores than patients who received mirabegron only. Interestingly, this previous study also showed that similar ACB scores were noted for patients with OAB who had received mirabegron only and patients without OAB. The authors concluded that these results showed that mirabegron could be used as an alternative to antimuscarinics to potentially reduce anticholinergic burden.
The increased ACB score in the OAB group is a troublesome finding given that previous investigations have noted specific associations between higher ACB scores and negative outcomes. For example, a one-point increase in total ACB score was associated with greater healthcare utilisation (number of inpatient admissions, outpatient visits, and emergency department visits) and a 13% increase in the risk of cognitive impairment in a large community-based study [22]. Furthermore, a 2-year UK study found that the use of anticholinergics that were included in the ACB scale was associated with cognitive impairment and increased mortality [23]. Given these findings, clinicians and policy stakeholders should consider an approach that minimises anticholinergic burden for patients with OAB.
The average age of patients who had received an OAB prescription was marginally higher than patients who had not (74.9 vs. 74.0 years). International geriatric guidelines recommend caution in prescribing antimuscarinic drugs to older patients owing to the risk of anticholinergic side effects in these individuals [24, 25]. Despite these recommendations, the previously mentioned Japanese pharmacy claims database investigation of patients with and without OAB found that prevalence of such prescriptions increased with age [21]. In our study, the highest proportion of patients aged ≥70 years was in the mirabegron-only group (79.0%) compared with the antimuscarinics with mirabegron group (76.7%) and antimuscarinics-only group (75.6%). The higher age for patients who receive mirabegron has been typically observed in previous database studies [26, 27], which may indicate that patients receive antimuscarinics before mirabegron in their treatment pathway or that mirabegron is being preferentially used in older patients, possibly due to concerns over anticholinergic burden or the risk of urinary retention [17, 21, 28].
Males constituted almost two-thirds of the patient cohort in both the OAB and non-OAB groups. This is higher than the proportions noted in other real-world studies of OAB, which generally report proportions of 50% or less [2, 3, 21, 26, 27, 29, 30]. In terms of the OAB cohort, the highest proportion of males was seen in the mirabegron-only group (67.8%) compared with the antimuscarinics-only group (61.9%) and antimuscarinics with mirabegron group (56.7%). This finding may be due to a preference for mirabegron over antimuscarinics in older men, who commonly have benign prostatic hyperplasia (BPH). As stated above, antimuscarinics are associated with an increased risk of urinary retention [17, 28], and may therefore be unsuitable for men with BPH due to the association of the condition with acute urinary retention [31]. Treatment guidelines recommend extreme caution when prescribing antimuscarinics to patients with a history of urinary retention [32].
The prevalence of dementia as a baseline comorbidity was ~10% higher in the OAB group compared with the non-OAB group and overall study population. The reason for this difference is unknown. However, it could be related to the slightly higher age of the patients in the OAB group or the presence of comorbidities that required treatment with drugs that are associated with cognitive impairment, which may have included the use of antimuscarinics more than 6 months before the start of the study. Importantly, anticholinergic medication may increase the risk of cognitive impairment, dementia, and mortality in older patients [10, 33]. A real-world study of patients with OAB in Canada found that use of anticholinergic medications was associated with increased risk of new-onset dementia when compared with mirabegron [30], and an analysis from a phase 4, randomised, placebo-controlled study showed that 12 weeks of mirabegron treatment was not associated with any increase in cognitive side effects in patients aged ≥65 years [34]. Therefore, mirabegron could be considered as a viable treatment option in patients with OAB and dementia.
The prevalence of chronic pulmonary disease at baseline was also ~10% higher in the OAB group compared with the non-OAB group. Previous studies have suggested an association between urinary incontinence and chronic pulmonary disease [35, 36]. It has been hypothesised that age-related changes in smooth muscle, increased abdominal pressure while coughing, and altered micturition control may explain the association between these two conditions, although the exact physiological mechanisms involved in this association remain to be elucidated [37]. In contrast, some clinical investigations have not observed a significant association between chronic pulmonary disease and OAB specifically [29, 38].
This study is subject to limitations inherent to its nature. Firstly, the definition that was used for OAB prescriptions during the 6 months leading to the index date and a 100-day follow-up period to measure cumulative ACB score may have restricted the number of potential patients with OAB who could be included in the study. However, our study still likely reflects the vast majority of the OAB population in South Korea. Secondly, despite the strengths of the ACB scale, it was developed in the US and may therefore include anticholinergics that are not approved in South Korea or vice versa, meaning the anticholinergic burden highlighted in this study may be a conservative estimate. Thirdly, this study did not examine the consequences of anticholinergic use on patient outcomes. Further research should investigate the side effect profile experienced by patients with OAB in South Korea following treatment with antimuscarinics or mirabegron.