In male patients with lower urinary tract symptoms (LUTS), α1 adrenergic receptor antagonists are sometimes effective in managing overactive bladder (OAB) symptoms. Further, studies of male patients with OAB showed the efficacies of the combination therapy of α1 adrenergic receptor antagonists and β3 adrenoceptor agonist or anticholinergic agent to the treatment regimen in patients with OAB symptoms that were refractory to α1 adrenergic receptor blockers.
However, there is currently no data on the effects of combining α1 adrenergic receptor antagonists and other drugs for treating OAB in female patients with LUTS. Therefore, the objective of this study was to clarify the effects of adding a β3 adrenoceptor agonist to the treatment regimen on OAB symptoms in women whose symptoms persisted after being treated for LUTS with an α1 adrenergic receptor antagonist.

This prospective, single-center, and open-label study was conducted in females who still met the diagnostic criteria for OAB after at least 3 months of continuous treatment for LUTS using oral urapidil. The patients were then administered a combination therapy of urapidil and mirabegron. 
The overactive bladder symptom score (OABSS) was used to subjectively assess symptoms, and uroflowmetry was used to objectively examine changes in symptoms at three-time points—before urapidil administration, when oral mirabegron (50 mg once daily) therapy was added, and after twelve weeks of administering mirabegron. A P value <0.05 was considered to indicate a statistically significant difference. 
The diagnostic criteria for OAB were scoring 2 points or higher on question 3 of the OABSS (urinary urgency) and 3 points or higher for the total OABSS score.

Overall, 109 subjects (mean age of 68.1±12.0 years) were included in the analysis. 
After urapidil administration, statistically significant improvements were observed in Q1 (daytime frequency), Q4 (urgency incontinence), and total OABSS score (Q1: P=0.020, Q4: P=0.009, total score: P=0.044). However, Q2 (nighttime frequency) and Q3 did not improve with urapidil administration (Q2: 2.3±0.6 to 2.3±0.8, P=0.990, Q3: 3.5±0.9 to 3.2±0.9, P=0.270). Conversely, twelve weeks after adding mirabegron to the treatment regimen, significant improvements were observed in all questions and the total OABSS score compared to before urapidil administration and when mirabegron therapy was added. After commencing the combination therapy comprising urapidil and mirabegron, 46 patients (42.2%) no longer met the diagnostic criteria for OAB. 
Regarding the objective assessment, voided volume significantly improved when initially using urapidil monotherapy from 127.0±67.8 ml to 156.2±74.9 ml; however, this increased further to 167.1±77.9 ml after adding mirabegron (P<0.001) to the treatment regimen. Both maximum flow rate (MFR, 10.9±4.8 ml/s to 13.6±5.2 ml/s) and post-void residual urine volume (PVR, 72.8±53.8 mL to 22.8±12.3 mL) improved significantly after commencing urapidil (both P<0.001). However, after adding mirabegron the changes in MFR (13.6±5.2 ml/s to 14.8±9.1 ml/s) and PVR (22.8 ±12.3 mL to 29.4±33.7 mL) were not statistically significant (MFR, P=0.844; PVR, P=0.289). During the observation period, no patients had to discontinue treatment due to adverse events.

This study suggests that urapidil monotherapy improves OAB symptoms to some extent.
In addition, oral mirabegron treatment for OAB symptoms which remained after urapidil therapy was effective and safe. In particular, after administration of mirabegron, all subjective symptoms related to OAB improved. Furthermore, in objective findings, the combined use of urapidil did not deteriorate urinary stream or PVR.

The addition of mirabegron after the administration of urapidil in patients with residual OAB symptoms, appears to be effective and safe without objective adverse events.