Stesura Seveso 451Archivio Italiano di Urologia e Andrologia 2022; 94, 4 ORIGINAL PAPER No conflict of interest declared. 11.8-24.7% of adults in North America and Europe, and its prevalence increases with age (3). In addition to age, the risk factors for OAB include diabetes, UTI, and obesi- ty (4, 5). Pharmacotherapy is the main treatment for OAB in Japan, and anticholinergic drugs are considered to be first-line drugs (6). Recently, β3 adrenergic agonists, which have completely different mechanism of action from anticholinergic drugs, have become available and have been shown to be effective. β3 adrenergic agonists were awarded a grade-A recom- mendation in the Japanese OAB treatment guidelines. However, no study on the criteria for choosing between anticholinergics and β3 adrenergic agonists has been published. When treating patients with OAB, how do cli- nicians choose among these medications, which both have grade-A recommendations and exhibit comparable therapeutic efficacy? Are there any factors that influence the selection of these medications? In the present study, we investigated the factors that influence the selection of anticholinergic drugs or β3 adrenergic agonists for OAB in the real world practice. MATERIALS AND METHODS This was a retrospective study, which used data extracted from electronic records. Seventy-five who were diagnosed with OAB at the Department of Urology, Teikyo University Chiba Medical Center (Ichihara, Japan), between January 2013 and December 2014 were included in this study. The Overactive Bladder Symptoms Score (OABSS) was cal- culated for each patient, and all of the patients met the diagnostic criteria for OAB. OAB was diagnosed based on the OABSS or the presence of urinary urgency (6). The OABSS is a validated self-assessed questionnaire cre- ated by the Japanese Continence Society and consists of four questions about OAB symptoms (Q1: daytime fre- quency, Q2: nighttime frequency, Q3: urgency, and Q4: urge incontinence) (6). We retrospectively evaluated various factors, including age, administered treatments, body mass index (BMI), pre- treatment total OABSS, pretreatment score for each OABSS factor, post-voiding residual volume (PVR), smok- ing habits, presence or absence of hypertension, diabetes mellitus, and dyslipidemia. The post-voiding residual (PVR) urine was measured on a transabdominal ultrasonic echogram in all cases. Objective: The reasons why anticholinergic drugs or β3 adrenergic agonists are selected as treatments for overactive bladder (OAB) are unclear. The aim of this study was to investigate the background data of female OAB patients that were prescribed anticholinergic drugs or β3 adrenergic agonists in a real-world setting. Materials and methods: Between January 2013 and December 2014, 75 patients who had been diagnosed with OAB were included in this study. Administered medications, age, the per- sistence on treatment rate at one-year, medical history, pre- treatment total Overactive Bladder Symptom Score (OABSS), pretreatment score for each OABSS factor, body mass index (BMI), and various comorbidities were evaluated retrospective- ly. Since there were many types of anticholinergic drugs and few patients, we grouped the patients into those that were prescribed anticholinergic drugs (group A) and those that were prescribed β3 adrenergic agonists (group B). Results: 75 patients (29 in group A and 46 in group B) were included in this study. There were no significant differences in age, BMI, obesity, medical history, pretreatment total OABSS, or pretreatment score for each OABSS factor. There was a sig- nificant difference in the post-voiding residual urine volume (PVR) between the groups (group A: 22 ml, group B: 9 ml; p = 0.0252). The 1-year persistence on treatment rate was 28% in both groups. Conclusions: There were no significant differences in clinical characteristics of patients who were prescribed anticholinergics and β3 adrenergic agonists for OAB treatment, but a marginal difference of PVR value before treatment. The 1-year persistence rates of anticholinergic drugs and β3 adrenergic agonists were considered to be almost equivalent. KEY WORDS: Overactive bladder; Anti-cholinergic drugs; β3 adrenergic agonists; Post-voiding residual urine volume. Submitted 28 October 2022; Accepted 10 November 2022 INTRODUCTION Overactive bladder (OAB) is a condition with characteris- tic symptoms of urinary urgency, usually accompanied by increased urinary frequency and nocturia, with or with- out urge incontinence, in the absence of a urinary tract infection (UTI) or any other obvious pathology (1). It was observed that the prevalence of OAB among Japanese adults aged ≥ 40 years is 12.4%, and the estimated num- ber of patients with OAB is 8.1 million (2). OAB affects The choice of therapeutic agent in female overactive bladder patients in real-world practice Hiroshi Masuda, Kosuke Mikami, Kotaro Otsuka, Kyokusin Hou, Takahito Suyama, Kazuhiro Araki, Satoko Kojima, Yukio Naya Department of Urology, Teikyo University Chiba Medical Center, 3426-3 Anesaki, Ichihara, Chiba 299-0111, Japan. DOI: 10.4081/aiua.2022.4.451 Summary Archivio Italiano di Urologia e Andrologia 2022; 94, 4 H. Masuda, K. Mikami, K. Otsuka, K. Hou, T. Suyama, K. Araki, S. Kojima, Y. Naya 452 Regarding the administered medications, since many kinds of anticholinergic drugs were administered in small groups of patients, patients were categorized into two groups as those treated with anticholinergic drugs (group A) and those treated with β3 adrenergic agonists (group B). The patients were allowed to discontinue their medication during the follow-up period, according to their desires and the judgement of the attending physician. We investigated the continuation/discontinuation of anticholinergic drug and β3 adrenergic agonist treatment. although we could not examine the reasons for discontinuation. Statistical analysis Statistical analyses were carried out to identify clinical parameters that differed significantly between groups A and B. The results are shown as mean ± SE or percentage. The Mann-Whitney U test and Chi-squared test were used for the statistical analyses. All analyses were per- formed with JMP version 10 (SAS Institute Inc., Cary, NC, USA). A probability value of < 0.05 was considered sta- tistically significant. Ethical approval. The institutional review board of Teikyo University approved this study (TUIC-COI 21-1218). RESULTS Table 1 shows the patients’ background characteristics. We evaluated 75 patients (29 in group A and 46 in group B) that were prescribed anticholinergic drugs or β3 adrenergic agonists by our department. There were no significant differences in age, BMI, obesi- ty, medical history, the pretreatment total OABSS, or the pretreatment scores for individual OABSS factors. The mean pretreatment PVR was significantly greater in group A than in group B (22 ml vs. 9 ml, respectively; P = 0.0252) (Table 2). A younger age, a lower pretreatment total OABSS score, Table 1. Patient characteristics. No. of patients N = 75 Age (years, mean ± SE) 70 ± 1.4 Medication Anticholinergics (N） 29 Propiverine 3 Imidafenacin 9 Fesoterodine 6 Solifenacin 11 β3 adrenergic agonists 46 Body mass index (kg/m2, mean ± SE) 28.2 ± 0.3 OABSS Daytime frequency 1.0 ± 0.1 Nighttime frequency 2.4 ± 0.1 Urgency 2.9 ± 0.2 Urge incontinence 1.7 ± 0.2 Total score 8.1 ± 0.5 PVR (ml, mean ± SE) 14 ± 2.6 Smoking Positive/Negative 7/68 Alcohol consumption Positive/Negative 7/68 Hypertension Positive/Negative 38/37 Diabetes mellitus Positive/Negative 10/65 Dyslipidemia Positive/Negative 24/51 OABSS: Overactive Bladder Symptom Score; PVR: Post-voiding residual urine volume. Table 2. Comparisons between the groups. Variable Group A (n = 29) Group B (n = 46) P-value Age (years, mean ± SE) 69 ± 1.4 71 ± 1.7 0.5029 Body mass index (kg/m2, mean ± SE) 28.2 ± 0.5 28.3 ± 0.3 0.6414 OABSS Daytime frequency 1.1 ± 0.1 1.0 ± 0.1 0.2736 Nighttime frequency 2.5 ± 0.1 2.4 ± 0.1 0.7708 Urgency 3.1 ± 0.2 2.8 ± 0.3 0.5017 Urge incontinence 2.1 ± 0.2 1.5 ± 0.3 0.1298 Total score 8.8 ± 0.7 7.7 ± 0.6 0.1639 PVR (ml, mean ± SE) 22 ± 5.8 9.2 ± 2.2 0.0247 0-50 ml/51-100 ml/100 ml< 26/3/0 45/1/0 0.1251 Smoking Positive/Negative 4/25 3/43 0.151 Alcohol consumption Positive/Negative 2/27 5/14 0.3061 Hypertension Positive/Negative 13/16 25/21 0.4219 Diabetes mellitus Positive/Negative 3/26 7/39 0.5455 Dyslipidemia Positive/Negative 7/22 17/29 0.2465 OABSS: Overactive Bladder Symptom Score; PVR: Post-voiding residual urine volume. Table 3. Assessment of the factors affecting the continuation of medical treatment. Variable Continuation Discontinuation P-value group (n = 21) group (n = 54) Age (years, mean ± SE) 74 ± 1.4 68 ± 1.7 0.2328 Medication 0.9495 Anticholinergics 8 21 Mirabegron 13 33 Body mass index (kg/m2, mean ± SE) 28.0 ± 0.5 28.3 ± 0.3 0.5236 OABSS Daytime frequency 1.2 ± 0.1 1.0 ± 0.1 0.201 Nighttime frequency 2.6 ± 0.3 2.4 ± 0.1 0.2912 Urgency 2.8 ± 0.4 3.0 ± 0.3 0.5301 Urge incontinence 1.9 ± 0.4 1.7 ± 0.3 0.614 Total score 8.6 ± 0.9 8.1 ± 0.5 0.8093 PVR (ml, mean ± SE) 18 ± 5.6 12 ± 3.0 0.3325 Smoking Positive/Negative 0/21 7/47 0.151 Alcohol consumption Positive/Negative 2/19 5/49 0.3061 Hypertension Positive/Negative 9/12 29/25 0.3989 Diabetes mellitus Positive/Negative 4/17 6/48 0.364 Dyslipidemia Positive/Negative 6/15 18/36 0.6914 OABSS: Overactive Bladder Symptom Score; PVR: Post-voiding residual urine volume. 453Archivio Italiano di Urologia e Andrologia 2022; 94, 4 Treatment in female OAB and a lower PVR were associated with a tendency towards medication discontinuation. However, no potential pre- dictors of discontinuation differed significantly between the groups (Table 3). The one-year persistence rate of pre- scriptions from our department was 28% in both groups. DISCUSSION In the Japanese guidelines for OAB, anticholinergic drugs and β3 adrenergic agonists are given grade-A recommen- dations as treatments for OAB (6). However, while there has been some debate about the usage of different anti- cholinergic drugs, there was insufficient discussion and there are no clear indicators or guidelines regarding the usage of anticholinergic drugs versus β3 adrenergic ago- nists. Therefore, individual medications are being adminis- tered for OAB without any particular reason in real-world practice, and it seems that choices between anticholinergic drugs and β3 adrenergic agonists are based on the treating doctor’s preferences and experience. In the present study, we investigated the factors that influence the selection of anticholinergic drugs and β3 adrenergic agonists in the real-world. To the best of our knowledge, this is the first study to investigate this among OAB patients. Safety Safety is the first consideration when selecting a drug, and avoiding adverse events should be prioritized over effica- cy. β3 adrenergic agonists cause side effects, such as dry mouth and constipation, less frequently than anticholin- ergic drugs. This should favor the selection of β3 adren- ergic agonists. Regarding dry mouth, it has been reported that β3 adrenergic agonists cause this symptom in 33% fewer cases than tolterodine (7). In another study, it was reported that the incidence of dry mouth during β3 adrenergic agonist treatment was similar to that produced by a placebo, and that it was associated in one-fifth of cases with anticholinergic drugs (8). It has been observed that dry mouth is an important factor influencing oral medication discontinuation (9). Therefore, there is an advantage in choosing β3 adrenergic agonists over anti- cholinergic drugs. It has also been reported that β3 adrenergic agonists have higher persistence rates than anticholinergics drugs and should be considered for first- line pharmacological treatment for OAB (10). Furthermore, it should be considered that elderly patients would be more likely to be prescribed β3 adrenergic ago- nists than anticholinergics because of their high frequen- cy of abnormal bowel movements. Finally, it is likely that medications that involve fewer oral doses should be selected for elderly patients because they may already be taking a large number of medications. Post-voiding residual urine In a comparative study of anticholinergic drugs and β3 adrenergic agonists, it was reported that there was no sig- nificant difference in the increase in the PVR seen during the study period (0.86 ml for the placebo, 0.80 ml for β3 adrenergic agonists, and 0.44 ml for tolterodine) (11). Moreover, Stöhrer et al. reported that the PVR increased significantly from 50 ml to 87 ml in patients treated with propiverine (12). Also, Khullar et al. reported that a PVR exceeding 300 ml was seen in 0.2% of patients treated with β3 adrenergic agonists (7). These studies suggest that the PVR is not a determining criterion during the selection of anticholinergic drugs or β3 adrenergic agonists. Regarding the frequency of urinary retention, it has been reported that it was < 1% in patients treated with anti- cholinergic drugs, while it was almost negligible in patients treated with β3 adrenergic agonists (13). In the present study the pretreatment PVR was signifi- cantly higher in patients who were prescribed anticholin- ergics compared to those who were treated with β3 adrenergic agonists, but this finding seemed to be of lim- ited clinical significance because it was related to only three patients with high PVR taking anticholinergics. Compliance to treatment It has been reported that the 1-year persistence rates of anticholinergic drugs and mirabegron ranged from 17% to 35% (14) and 19-38% (9, 15, 16), respectively. The 1-year persistence rates of anticholinergic drugs and β3 adrenergic agonists at our institution were similar. It has been reported that treatment discontinuation is also seen in younger age groups, and our study showed a sim- ilar trend (17). We suggest that this could be explained by the fact that the drugs were administered at hospital, and an appoint- ment was required to visit the hospital. However, a recent study suggested that β3 adrenergic agonists have very high 1-year persistence rates of 63% in females and 67% in males (18). It was considered that this was probably because β3 adrenergic agonists are safe and well tolerated. Non-medical factors Recently, a study reported that when physicians received complimentary meals and hospitality by a pharmaceutical company they increased their prescriptions of drugs mar- keted by that company (19). Although this may have affected our prescription patterns, we do not have any information about this in the present study. This could be an important subject for further study, including other oral medications. Limitations Our study presented some limitations: 1) It was a retrospective cohort study, which involved the extraction of electronically stored clinical data, and it had a small sample size. Thus, it will be necessary to validate the findings of this retrospective analysis in prospective stud- ies, including a randomized study, with larger populations in future. We expect that such studies will provide new perspectives on how decisions regarding the selection of anticholinergic drugs and β3 adrenergic agonists are made. 2) Since this study only involved females, the factors influ- encing the selection of anticholinergic drugs or β3 adren- ergic agonists in male OAB patients were not evaluated. 3) The patients’ complications and the other types of medications they were taking were not investigated, and hence, more detailed patient background information is needed. 4) The two-year observation period was relatively short, Archivio Italiano di Urologia e Andrologia 2022; 94, 4 H. Masuda, K. Mikami, K. Otsuka, K. Hou, T. Suyama, K. Araki, S. Kojima, Y. Naya 454 and hence, it may not have been long enough to allow appropriate evaluations to be performed. 5) Patients assuming anticholinergics were analyzed col- lectively because the small number of patients taking dif- ferent anticholinergics did not allow to analyze them sep- arately. Collection of larger populations taking different anticholinergics could give information about difference of outcomes between them. 6) Untreated patients were not investigated. 7) We did not investigate refractory OAB separately. CONCLUSIONS There were no significant differences in clinical charac- teristics of patients who were prescribed anticholinergics and β3 adrenergic agonists for OAB treatment, but a mar- ginal difference of PVR value before treatment. The 1-year persistence rates of anticholinergic drugs and β3 adrenergic agonists were considered to be almost equiv- alent. REFERENCES 1. Abrams P, Cardozo L, Fall M Paul Abrams, et al. 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Correspondence Hiroshi Masuda, MD, PhD (Corresponding Author) hrsmasuda@yahoo.co.jp Kosuke Mikami, MD Kotaro Otsuka, MD Kyokusin Hou, MD Takahito Suyama, MD Kazuhiro Araki, MD Satoko Kojima, MD Yukio Naya, MD Department of Urology, Teikyo University Chiba Medical Center, 3426-3 Anesaki, Ichihara, Chiba, 299-0111, Japan